TY  - JOUR
AU  - Milanović, Desanka
AU  - Perović, Milka
AU  - Petrović, Snježana
AU  - Todorović, Smilja
AU  - Prvulović, Milica
AU  - Vukojević, Anđela
AU  - Mladenović, Aleksandra
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6699
AB  - Omega-3 fatty acid interventions show potential benefits in Alzheimer’s disease (AD) when initiated during its early stages. This study investigated whether maternal diet supplemented with omega- 3-rich fish oil (FO) could delay or reduce amyloid beta (Aβ) formation, a key feature of AD, in 5xFAD transgenic offspring. Dams received FO during mating, pregnancy, and lactation. Brain tissues from female offspring were collected at 2 and 6 months of age. The findings indicated a shift in amyloid precursor protein processing, evidenced by increased soluble amyloid precursor protein α (sAPPα) levels, suggesting a transition from amyloidogenic to non-amyloidogenic pathway. FO influenced the expression of presenilin 1 and 2 but did not impact Aβ levels in 2-month-old mice. However, FO reduced the Aβ burden in the brains of 6-month-old animals. Lipidomic analysis revealed that 5xFAD mice have unimpaired omega-3 acquisition during gestation and lactation in comparison to non-transgenic littermates. However, a response to FO supplementation was found in non-transgenic offspring only, indicating that alterations in brain lipids are not the primary mechanism of FO-induced Aβ decline in 5xFAD. In conclusion, FO did not prevent or delay amyloid pathology in genetically predisposed animals but did mitigate its progression, suggesting mechanisms that warrant further investigation.
PB  - Belgrade: Serbian Biological Society
T2  - Archives of Biological Sciences
T1  - Maternal fish-oil supplementation reduces presenilin 1 level and the amyloid-beta burden in adult 5xFAD offspring without major changes in brain fatty acids
IS  - 1
VL  - 76
DO  - 10.2298/ABS240105001M
SP  - 41
EP  - 53
ER  - 

@article{
author = "Milanović, Desanka and Perović, Milka and Petrović, Snježana and Todorović, Smilja and Prvulović, Milica and Vukojević, Anđela and Mladenović, Aleksandra",
year = "2024",
abstract = "Omega-3 fatty acid interventions show potential benefits in Alzheimer’s disease (AD) when initiated during its early stages. This study investigated whether maternal diet supplemented with omega- 3-rich fish oil (FO) could delay or reduce amyloid beta (Aβ) formation, a key feature of AD, in 5xFAD transgenic offspring. Dams received FO during mating, pregnancy, and lactation. Brain tissues from female offspring were collected at 2 and 6 months of age. The findings indicated a shift in amyloid precursor protein processing, evidenced by increased soluble amyloid precursor protein α (sAPPα) levels, suggesting a transition from amyloidogenic to non-amyloidogenic pathway. FO influenced the expression of presenilin 1 and 2 but did not impact Aβ levels in 2-month-old mice. However, FO reduced the Aβ burden in the brains of 6-month-old animals. Lipidomic analysis revealed that 5xFAD mice have unimpaired omega-3 acquisition during gestation and lactation in comparison to non-transgenic littermates. However, a response to FO supplementation was found in non-transgenic offspring only, indicating that alterations in brain lipids are not the primary mechanism of FO-induced Aβ decline in 5xFAD. In conclusion, FO did not prevent or delay amyloid pathology in genetically predisposed animals but did mitigate its progression, suggesting mechanisms that warrant further investigation.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Archives of Biological Sciences",
title = "Maternal fish-oil supplementation reduces presenilin 1 level and the amyloid-beta burden in adult 5xFAD offspring without major changes in brain fatty acids",
number = "1",
volume = "76",
doi = "10.2298/ABS240105001M",
pages = "41-53"
}

Milanović, D., Perović, M., Petrović, S., Todorović, S., Prvulović, M., Vukojević, A.,& Mladenović, A.. (2024). Maternal fish-oil supplementation reduces presenilin 1 level and the amyloid-beta burden in adult 5xFAD offspring without major changes in brain fatty acids. in Archives of Biological Sciences
Belgrade: Serbian Biological Society., 76(1), 41-53.
https://doi.org/10.2298/ABS240105001M

Milanović D, Perović M, Petrović S, Todorović S, Prvulović M, Vukojević A, Mladenović A. Maternal fish-oil supplementation reduces presenilin 1 level and the amyloid-beta burden in adult 5xFAD offspring without major changes in brain fatty acids. in Archives of Biological Sciences. 2024;76(1):41-53.
doi:10.2298/ABS240105001M .

Milanović, Desanka, Perović, Milka, Petrović, Snježana, Todorović, Smilja, Prvulović, Milica, Vukojević, Anđela, Mladenović, Aleksandra, "Maternal fish-oil supplementation reduces presenilin 1 level and the amyloid-beta burden in adult 5xFAD offspring without major changes in brain fatty acids" in Archives of Biological Sciences, 76, no. 1 (2024):41-53,
https://doi.org/10.2298/ABS240105001M . .

TY  - JOUR
AU  - Prvulović, Milica
AU  - Sokanović, Srđan
AU  - Simeunović, Valentina
AU  - Vukojević, Anđela
AU  - Jović, Milena
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6585
AB  - Age-related reduction in spine density, synaptic marker expression, and synaptic efficiency are frequently reported. These changes provide the cellular and
molecular basis for the cognitive decline characteristic for old age. Nevertheless, there are several approaches that have the potential to ameliorate these
processes and improve cognition, caloric restriction being one of the most
promising and widely studied. While lifelong caloric restriction is known for
its numerous beneficial effects, including improved cognitive abilities and
increased expression of proteins essential for synaptic structure and function,
the effects of late-onset and/or short-term CR on synaptic plasticity have yet to
be investigated. We have previously documented that the effects of CR are
strongly dependent on whether CR is initiated in young or old subjects. With
this in mind, we conducted a long-term study in aging Wistar rats to examine
changes in the expression of several key synaptic markers under the regimen
of CR started at different time points in life. We found a significant increase in
the expression of both presynaptic and postsynaptic markers. However, taking
into account previously reported changes in the behavior detected in these animals, we consider that this increase cannot represent beneficial effect of CR.
PB  - John Wiley and Sons
T2  - IUBMB Life
T1  - The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats
DO  - 10.1002/iub.2812
ER  - 

@article{
author = "Prvulović, Milica and Sokanović, Srđan and Simeunović, Valentina and Vukojević, Anđela and Jović, Milena and Todorović, Smilja and Mladenović, Aleksandra",
year = "2024",
abstract = "Age-related reduction in spine density, synaptic marker expression, and synaptic efficiency are frequently reported. These changes provide the cellular and
molecular basis for the cognitive decline characteristic for old age. Nevertheless, there are several approaches that have the potential to ameliorate these
processes and improve cognition, caloric restriction being one of the most
promising and widely studied. While lifelong caloric restriction is known for
its numerous beneficial effects, including improved cognitive abilities and
increased expression of proteins essential for synaptic structure and function,
the effects of late-onset and/or short-term CR on synaptic plasticity have yet to
be investigated. We have previously documented that the effects of CR are
strongly dependent on whether CR is initiated in young or old subjects. With
this in mind, we conducted a long-term study in aging Wistar rats to examine
changes in the expression of several key synaptic markers under the regimen
of CR started at different time points in life. We found a significant increase in
the expression of both presynaptic and postsynaptic markers. However, taking
into account previously reported changes in the behavior detected in these animals, we consider that this increase cannot represent beneficial effect of CR.",
publisher = "John Wiley and Sons",
journal = "IUBMB Life",
title = "The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats",
doi = "10.1002/iub.2812"
}

Prvulović, M., Sokanović, S., Simeunović, V., Vukojević, A., Jović, M., Todorović, S.,& Mladenović, A.. (2024). The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats. in IUBMB Life
John Wiley and Sons..
https://doi.org/10.1002/iub.2812

Prvulović M, Sokanović S, Simeunović V, Vukojević A, Jović M, Todorović S, Mladenović A. The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats. in IUBMB Life. 2024;.
doi:10.1002/iub.2812 .

Prvulović, Milica, Sokanović, Srđan, Simeunović, Valentina, Vukojević, Anđela, Jović, Milena, Todorović, Smilja, Mladenović, Aleksandra, "The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats" in IUBMB Life (2024),
https://doi.org/10.1002/iub.2812 . .

TY  - JOUR
AU  - Prvulović, Milica
AU  - Sokanović, Srđan
AU  - Simeunović, Valentina
AU  - Vukojević, Anđela
AU  - Jović, Milena
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6586
AB  - Age-related reduction in spine density, synaptic marker expression, and synaptic efficiency are frequently reported. These changes provide the cellular andmolecular basis for the cognitive decline characteristic for old age. Nevertheless, there are several approaches that have the potential to ameliorate theseprocesses and improve cognition, caloric restriction being one of the mostpromising and widely studied. While lifelong caloric restriction is known forits numerous beneficial effects, including improved cognitive abilities andincreased expression of proteins essential for synaptic structure and function,the effects of late-onset and/or short-term CR on synaptic plasticity have yet tobe investigated. We have previously documented that the effects of CR arestrongly dependent on whether CR is initiated in young or old subjects. Withthis in mind, we conducted a long-term study in aging Wistar rats to examinechanges in the expression of several key synaptic markers under the regimenof CR started at different time points in life. We found a significant increase inthe expression of both presynaptic and postsynaptic markers. However, takinginto account previously reported changes in the behavior detected in these animals, we consider that this increase cannot represent beneficial effect of CR.
PB  - John Wiley and Sons
T2  - IUBMB Life
T1  - The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats
DO  - 10.1002/iub.2812
ER  - 

@article{
author = "Prvulović, Milica and Sokanović, Srđan and Simeunović, Valentina and Vukojević, Anđela and Jović, Milena and Todorović, Smilja and Mladenović, Aleksandra",
year = "2024",
abstract = "Age-related reduction in spine density, synaptic marker expression, and synaptic efficiency are frequently reported. These changes provide the cellular andmolecular basis for the cognitive decline characteristic for old age. Nevertheless, there are several approaches that have the potential to ameliorate theseprocesses and improve cognition, caloric restriction being one of the mostpromising and widely studied. While lifelong caloric restriction is known forits numerous beneficial effects, including improved cognitive abilities andincreased expression of proteins essential for synaptic structure and function,the effects of late-onset and/or short-term CR on synaptic plasticity have yet tobe investigated. We have previously documented that the effects of CR arestrongly dependent on whether CR is initiated in young or old subjects. Withthis in mind, we conducted a long-term study in aging Wistar rats to examinechanges in the expression of several key synaptic markers under the regimenof CR started at different time points in life. We found a significant increase inthe expression of both presynaptic and postsynaptic markers. However, takinginto account previously reported changes in the behavior detected in these animals, we consider that this increase cannot represent beneficial effect of CR.",
publisher = "John Wiley and Sons",
journal = "IUBMB Life",
title = "The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats",
doi = "10.1002/iub.2812"
}

Prvulović, M., Sokanović, S., Simeunović, V., Vukojević, A., Jović, M., Todorović, S.,& Mladenović, A.. (2024). The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats. in IUBMB Life
John Wiley and Sons..
https://doi.org/10.1002/iub.2812

Prvulović M, Sokanović S, Simeunović V, Vukojević A, Jović M, Todorović S, Mladenović A. The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats. in IUBMB Life. 2024;.
doi:10.1002/iub.2812 .

Prvulović, Milica, Sokanović, Srđan, Simeunović, Valentina, Vukojević, Anđela, Jović, Milena, Todorović, Smilja, Mladenović, Aleksandra, "The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats" in IUBMB Life (2024),
https://doi.org/10.1002/iub.2812 . .

TY  - CONF
AU  - Simeunović, Valentina
AU  - Todorović, Smilja
AU  - Prvulović, Milica
AU  - Sokanović, Srđan
AU  - Jović, Milena
AU  - Vukojević, Anđela
AU  - Milanović, Desanka
AU  - Mladenović, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5807
AB  - Dietary restriction (DR) is one of the most studied environmental factors, which has 
been shown to prolong life and enhance health. However, the outcome of DR depends 
on both the duration of DR as well as the age of the individual at the onset of food 
restriction. A few studies have been conducted on the impacts of DR during puberty, 
but mainly casting doubt on beneficial effects it has on the individual. 
In this experiment we studied the effect of 30% DR (70% of ad libitum daily intake) 
during puberty on locomotor and vertical activity of 6- and 18-month-old female 
Wistar rats. We examined the effects of DR of different onsets and durations: first one 
that lasted from 28th to 35th day of life (Early Diet, ED), second lasted from 35th to 
42nd day of life (Late Diet, LD), and the one that lasted from 28th to 42nd day of life 
(Combined Diet, CD). The Open Field Test was used for tracking locomotor and 
vertical activity.
Our findings demonstrated that in 6-month-old females all three types of DR 
increased locomotor and vertical movement. Although the impact of DR during 
puberty is evident in adults, it is lost during aging, as older animals showed no 
significant change in locomotor or vertical activity under any type of DR.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Dietary restriction during puberty changes locomotor and vertical  activity of adult female Wistar rats in an onset- and duration-dependent manner
SP  - 69
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5807
ER  - 

@conference{
author = "Simeunović, Valentina and Todorović, Smilja and Prvulović, Milica and Sokanović, Srđan and Jović, Milena and Vukojević, Anđela and Milanović, Desanka and Mladenović, Aleksandra",
year = "2023",
abstract = "Dietary restriction (DR) is one of the most studied environmental factors, which has 
been shown to prolong life and enhance health. However, the outcome of DR depends 
on both the duration of DR as well as the age of the individual at the onset of food 
restriction. A few studies have been conducted on the impacts of DR during puberty, 
but mainly casting doubt on beneficial effects it has on the individual. 
In this experiment we studied the effect of 30% DR (70% of ad libitum daily intake) 
during puberty on locomotor and vertical activity of 6- and 18-month-old female 
Wistar rats. We examined the effects of DR of different onsets and durations: first one 
that lasted from 28th to 35th day of life (Early Diet, ED), second lasted from 35th to 
42nd day of life (Late Diet, LD), and the one that lasted from 28th to 42nd day of life 
(Combined Diet, CD). The Open Field Test was used for tracking locomotor and 
vertical activity.
Our findings demonstrated that in 6-month-old females all three types of DR 
increased locomotor and vertical movement. Although the impact of DR during 
puberty is evident in adults, it is lost during aging, as older animals showed no 
significant change in locomotor or vertical activity under any type of DR.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Dietary restriction during puberty changes locomotor and vertical  activity of adult female Wistar rats in an onset- and duration-dependent manner",
pages = "69",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5807"
}

Simeunović, V., Todorović, S., Prvulović, M., Sokanović, S., Jović, M., Vukojević, A., Milanović, D.,& Mladenović, A.. (2023). Dietary restriction during puberty changes locomotor and vertical  activity of adult female Wistar rats in an onset- and duration-dependent manner. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 69.
https://hdl.handle.net/21.15107/rcub_ibiss_5807

Simeunović V, Todorović S, Prvulović M, Sokanović S, Jović M, Vukojević A, Milanović D, Mladenović A. Dietary restriction during puberty changes locomotor and vertical  activity of adult female Wistar rats in an onset- and duration-dependent manner. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:69.
https://hdl.handle.net/21.15107/rcub_ibiss_5807 .

Simeunović, Valentina, Todorović, Smilja, Prvulović, Milica, Sokanović, Srđan, Jović, Milena, Vukojević, Anđela, Milanović, Desanka, Mladenović, Aleksandra, "Dietary restriction during puberty changes locomotor and vertical  activity of adult female Wistar rats in an onset- and duration-dependent manner" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):69,
https://hdl.handle.net/21.15107/rcub_ibiss_5807 .

TY  - CONF
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Milanović, Desanka
AU  - Simeunović, Valentina
AU  - Vukojević, Anđela
AU  - Jović, Milena
AU  - Sokanović, Srđan
AU  - Mladenović, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6408
AB  - Although delaying age-related changes is a recognized effect of
caloric restriction (CR), its duration along with a person's age and
sex, can significantly alter its protective potential and even have a
detrimental effect when implemented later in life. One of the
underlying mechanisms of the effect of CR on aging may be through
the mTOR pathway, as its important role in nutrient sensing and
regulation of cellular metabolism is well known. We investigated the
expression of key molecules of this signaling pathway during aging
and under different CR regimens. Male Wistar rats of different ages
(adult, middle-aged, and old) were exposed to CR (60% of AL) to
study the effect of CR at early (EOCR) and at late onset (LOCR). Ad
libitum (AL) fed animals were used to test the effects of aging and as
age-matched controls for the effect of CR. Western blot was used to
analyze the expression of proteins involved in the signaling cascade
and the interaction of mTOR complexes 1 and 2 (mTORC1,
mTORC2) in rat cortex. At 18 months of age, both EOCR and LOCR
led to a decrease in phosphorylation of mTOR S2448, which is
mainly associated with MTORC1, whereas LOCR led to an increase at
24 months of age. Phosphorylation of mTOR S2481 (mainly asso ciated with mTORC2) increased with age, whereas LOCR resulted in
a decrease at both ages. Although both EOCR and LOCR led to a
decrease in phosphorylation of mTOR at 18 months of age, some
effects were lost at 24 months. Changes in the expression of two
different phosphorylated forms of AKT responsible for communica tion between MTORC1 and MTORC2 were inconsistent, suggesting that another kinase may be responsible for mTOR phosphorylation
without affecting AKT.
PB  - Elsevier
C3  - IBRO 11th World Congress of Neuroscience; 2023 Sep 9-13; Granada, Spain
T1  - mTOR signaling pathway changes under the effect of caloric restriction in the cortex of male Wistar rats
DO  - 10.1016/j.ibneur.2023.08.932
SP  - S478
ER  - 

@conference{
author = "Prvulović, Milica and Todorović, Smilja and Milanović, Desanka and Simeunović, Valentina and Vukojević, Anđela and Jović, Milena and Sokanović, Srđan and Mladenović, Aleksandra",
year = "2023",
abstract = "Although delaying age-related changes is a recognized effect of
caloric restriction (CR), its duration along with a person's age and
sex, can significantly alter its protective potential and even have a
detrimental effect when implemented later in life. One of the
underlying mechanisms of the effect of CR on aging may be through
the mTOR pathway, as its important role in nutrient sensing and
regulation of cellular metabolism is well known. We investigated the
expression of key molecules of this signaling pathway during aging
and under different CR regimens. Male Wistar rats of different ages
(adult, middle-aged, and old) were exposed to CR (60% of AL) to
study the effect of CR at early (EOCR) and at late onset (LOCR). Ad
libitum (AL) fed animals were used to test the effects of aging and as
age-matched controls for the effect of CR. Western blot was used to
analyze the expression of proteins involved in the signaling cascade
and the interaction of mTOR complexes 1 and 2 (mTORC1,
mTORC2) in rat cortex. At 18 months of age, both EOCR and LOCR
led to a decrease in phosphorylation of mTOR S2448, which is
mainly associated with MTORC1, whereas LOCR led to an increase at
24 months of age. Phosphorylation of mTOR S2481 (mainly asso ciated with mTORC2) increased with age, whereas LOCR resulted in
a decrease at both ages. Although both EOCR and LOCR led to a
decrease in phosphorylation of mTOR at 18 months of age, some
effects were lost at 24 months. Changes in the expression of two
different phosphorylated forms of AKT responsible for communica tion between MTORC1 and MTORC2 were inconsistent, suggesting that another kinase may be responsible for mTOR phosphorylation
without affecting AKT.",
publisher = "Elsevier",
journal = "IBRO 11th World Congress of Neuroscience; 2023 Sep 9-13; Granada, Spain",
title = "mTOR signaling pathway changes under the effect of caloric restriction in the cortex of male Wistar rats",
doi = "10.1016/j.ibneur.2023.08.932",
pages = "S478"
}

Prvulović, M., Todorović, S., Milanović, D., Simeunović, V., Vukojević, A., Jović, M., Sokanović, S.,& Mladenović, A.. (2023). mTOR signaling pathway changes under the effect of caloric restriction in the cortex of male Wistar rats. in IBRO 11th World Congress of Neuroscience; 2023 Sep 9-13; Granada, Spain
Elsevier., S478.
https://doi.org/10.1016/j.ibneur.2023.08.932

Prvulović M, Todorović S, Milanović D, Simeunović V, Vukojević A, Jović M, Sokanović S, Mladenović A. mTOR signaling pathway changes under the effect of caloric restriction in the cortex of male Wistar rats. in IBRO 11th World Congress of Neuroscience; 2023 Sep 9-13; Granada, Spain. 2023;:S478.
doi:10.1016/j.ibneur.2023.08.932 .

Prvulović, Milica, Todorović, Smilja, Milanović, Desanka, Simeunović, Valentina, Vukojević, Anđela, Jović, Milena, Sokanović, Srđan, Mladenović, Aleksandra, "mTOR signaling pathway changes under the effect of caloric restriction in the cortex of male Wistar rats" in IBRO 11th World Congress of Neuroscience; 2023 Sep 9-13; Granada, Spain (2023):S478,
https://doi.org/10.1016/j.ibneur.2023.08.932 . .

TY  - JOUR
AU  - Todorović, Smilja
AU  - Simeunović, Valentina
AU  - Prvulović, Milica
AU  - Dakić, Tamara
AU  - Jevđović, Tanja
AU  - Sokanović, Srđan
AU  - Kanazir, Selma
AU  - Mladenović, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6373
AB  - Insulin is known to be a key hormone in the regulation of peripheral glucose homeostasis, but beyond that, its effects on the brain are now undisputed. Impairments in insulin signaling in the brain, including changes in insulin levels, are thought to contribute significantly to declines in cognitive performance, especially during aging. As one of the most widely studied experimental interventions, dietary restriction (DR) is considered to delay the neurodegenerative processes associated with aging. Recently, however, data began to suggest that the onset and duration of a restrictive diet play a critical role in the putative beneficial outcome. Because the effects of DR on insulin signaling in the brain have been poorly studied, we decided to examine the effects of DR that differed in onset and duration: long-term DR (LTDR), medium-term DR (MTDR), and short-term DR (STDR) on the expression of proteins involved in insulin signaling in the hippocampus of 18- and 24-month-old male Wistar rats. We found that DR-induced changes in insulin levels in the brain may be independent of what happens in the periphery after restricted feeding. Significantly changed insulin content in the hippocampus, together with altered insulin signaling were found under the influence of DR, but the outcome was highly dependent on the onset and duration of DR.
PB  - Hoboken: John Wiley and Sons
T2  - Biofactors
T1  - Dietary restriction alters insulin signaling pathway in the brain
DO  - 10.1002/biof.2018
ER  - 

@article{
author = "Todorović, Smilja and Simeunović, Valentina and Prvulović, Milica and Dakić, Tamara and Jevđović, Tanja and Sokanović, Srđan and Kanazir, Selma and Mladenović, Aleksandra",
year = "2023",
abstract = "Insulin is known to be a key hormone in the regulation of peripheral glucose homeostasis, but beyond that, its effects on the brain are now undisputed. Impairments in insulin signaling in the brain, including changes in insulin levels, are thought to contribute significantly to declines in cognitive performance, especially during aging. As one of the most widely studied experimental interventions, dietary restriction (DR) is considered to delay the neurodegenerative processes associated with aging. Recently, however, data began to suggest that the onset and duration of a restrictive diet play a critical role in the putative beneficial outcome. Because the effects of DR on insulin signaling in the brain have been poorly studied, we decided to examine the effects of DR that differed in onset and duration: long-term DR (LTDR), medium-term DR (MTDR), and short-term DR (STDR) on the expression of proteins involved in insulin signaling in the hippocampus of 18- and 24-month-old male Wistar rats. We found that DR-induced changes in insulin levels in the brain may be independent of what happens in the periphery after restricted feeding. Significantly changed insulin content in the hippocampus, together with altered insulin signaling were found under the influence of DR, but the outcome was highly dependent on the onset and duration of DR.",
publisher = "Hoboken: John Wiley and Sons",
journal = "Biofactors",
title = "Dietary restriction alters insulin signaling pathway in the brain",
doi = "10.1002/biof.2018"
}

Todorović, S., Simeunović, V., Prvulović, M., Dakić, T., Jevđović, T., Sokanović, S., Kanazir, S.,& Mladenović, A.. (2023). Dietary restriction alters insulin signaling pathway in the brain. in Biofactors
Hoboken: John Wiley and Sons..
https://doi.org/10.1002/biof.2018

Todorović S, Simeunović V, Prvulović M, Dakić T, Jevđović T, Sokanović S, Kanazir S, Mladenović A. Dietary restriction alters insulin signaling pathway in the brain. in Biofactors. 2023;.
doi:10.1002/biof.2018 .

Todorović, Smilja, Simeunović, Valentina, Prvulović, Milica, Dakić, Tamara, Jevđović, Tanja, Sokanović, Srđan, Kanazir, Selma, Mladenović, Aleksandra, "Dietary restriction alters insulin signaling pathway in the brain" in Biofactors (2023),
https://doi.org/10.1002/biof.2018 . .

TY  - CONF
AU  - Mladenović, Aleksandra
AU  - Prvulović, Milica
AU  - Milanović, Desanka
AU  - Sokanović, Srđan
AU  - Vukojević, Anđela
AU  - Simeunović, Valentina
AU  - Kanazir, Selma
AU  - Todorović, Smilja
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5852
AB  - Dietary restriction (DR) is considered the gold standard in anti-aging treatment. Since 
the first study on the beneficial effects of DR in 1935, countless research articles have 
demonstrated numerous positive effects of DR. DR is often referred to as the elixir of 
youth due to its proven ability to extend lifespan in various species. The beneficial 
effects of DR are observed in many organ systems, including the prevention of age related diabetes and the reduction of the occurrence and progression of various 
cancers, the improvement of various cardiovascular risk factors, and the delay of 
osteoporosis and sarcopenia. As for the effects of DR on the nervous system, 
numerous neuroprotective effects have been noted, such as the ability to preserve
cognition, delay brain atrophy, and protect against various neurodegenerative diseases. 
By applying long-term dietary restriction during adulthood in male and female Wistar 
rats, we demonstrated several beneficial results. DR increased the levels of synaptic 
plasticity markers and neurotrophic factors in rat cortex and hippocampus and 
preserved brain cholesterol homeostasis during aging. In addition, it suppressed 
apoptotic cell death after cortical injury and restored age-related impaired 
glucocorticoid receptor signaling (GR) in the brain. DR also demonstrated the ability 
to alter the expression of genes involved in the pathology of AD and to suppress 
microglial activation after cortical injury. Equally important, however, we found that 
DR can also have negative effects depending on the age at which it was introduced 
and the duration of treatment. Namely, we demonstrated that short-term 
administration of DR at older ages had unfavorable effects on cognitive performance, 
anxiety levels, and frailty in Wistar rats. In addition, DR showed some adverse effects 
in transgenic AD animals. The results of our studies urge great caution in the 
introduction of DR in humans, as the feasibility, safety, and adverse effects of DR as 
an anti-aging measure in human populations have not been fully elucidated. To 
achieve a positive effect, it is important to ensure that DR is used in a manner that 
meets the nutritional needs of people of all ages.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Dietary restriction as an anti-aging intervention
SP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5852
ER  - 

@conference{
author = "Mladenović, Aleksandra and Prvulović, Milica and Milanović, Desanka and Sokanović, Srđan and Vukojević, Anđela and Simeunović, Valentina and Kanazir, Selma and Todorović, Smilja",
year = "2023",
abstract = "Dietary restriction (DR) is considered the gold standard in anti-aging treatment. Since 
the first study on the beneficial effects of DR in 1935, countless research articles have 
demonstrated numerous positive effects of DR. DR is often referred to as the elixir of 
youth due to its proven ability to extend lifespan in various species. The beneficial 
effects of DR are observed in many organ systems, including the prevention of age related diabetes and the reduction of the occurrence and progression of various 
cancers, the improvement of various cardiovascular risk factors, and the delay of 
osteoporosis and sarcopenia. As for the effects of DR on the nervous system, 
numerous neuroprotective effects have been noted, such as the ability to preserve
cognition, delay brain atrophy, and protect against various neurodegenerative diseases. 
By applying long-term dietary restriction during adulthood in male and female Wistar 
rats, we demonstrated several beneficial results. DR increased the levels of synaptic 
plasticity markers and neurotrophic factors in rat cortex and hippocampus and 
preserved brain cholesterol homeostasis during aging. In addition, it suppressed 
apoptotic cell death after cortical injury and restored age-related impaired 
glucocorticoid receptor signaling (GR) in the brain. DR also demonstrated the ability 
to alter the expression of genes involved in the pathology of AD and to suppress 
microglial activation after cortical injury. Equally important, however, we found that 
DR can also have negative effects depending on the age at which it was introduced 
and the duration of treatment. Namely, we demonstrated that short-term 
administration of DR at older ages had unfavorable effects on cognitive performance, 
anxiety levels, and frailty in Wistar rats. In addition, DR showed some adverse effects 
in transgenic AD animals. The results of our studies urge great caution in the 
introduction of DR in humans, as the feasibility, safety, and adverse effects of DR as 
an anti-aging measure in human populations have not been fully elucidated. To 
achieve a positive effect, it is important to ensure that DR is used in a manner that 
meets the nutritional needs of people of all ages.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Dietary restriction as an anti-aging intervention",
pages = "34",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5852"
}

Mladenović, A., Prvulović, M., Milanović, D., Sokanović, S., Vukojević, A., Simeunović, V., Kanazir, S.,& Todorović, S.. (2023). Dietary restriction as an anti-aging intervention. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 34.
https://hdl.handle.net/21.15107/rcub_ibiss_5852

Mladenović A, Prvulović M, Milanović D, Sokanović S, Vukojević A, Simeunović V, Kanazir S, Todorović S. Dietary restriction as an anti-aging intervention. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:34.
https://hdl.handle.net/21.15107/rcub_ibiss_5852 .

Mladenović, Aleksandra, Prvulović, Milica, Milanović, Desanka, Sokanović, Srđan, Vukojević, Anđela, Simeunović, Valentina, Kanazir, Selma, Todorović, Smilja, "Dietary restriction as an anti-aging intervention" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):34,
https://hdl.handle.net/21.15107/rcub_ibiss_5852 .

TY  - CONF
AU  - Jović, Milena
AU  - Simeunović, Valentina
AU  - Vukojević, Anđela
AU  - Prvulović, Milica
AU  - Sokanović, Srđan
AU  - Mladenović, Aleksandra
AU  - Milanović, Desanka
AU  - Todorović, Smilja
AU  - Lončarević-Vasiljković, Nataša
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5851
AB  - According to the amyloid hypothesis of Alcheimer’s disease (AD), disruption of 
balance between production and clearance of Aβ from the cells leads to the 
progressive accumulation and aggregation of amyloid beta (Aβ) peptides in the brain. 
The glial system (microglial cells and astrocytes) is responsible for maintaining 
homeostasis in the brain which implies its important role in the development and 
progression of AD. Our previous work revealed that the short-term fish oil (FO) 
treatment in 5xFAD mice, (AD animal model), reduces toxic Aβ load and increases 
number of microglial/macrophage cells in parietal cortex. In the present study we 
aimed to further decipher the roles of microglial and macrophage cells and to 
elucidate possible mechanisms responsible for observed reduced level of toxic Aβ42 
peptide. For this purpose, western blot and immunohistochemical analysis were used 
to detect changes in parietal cortex of three-month-old 5xFAD mice after three weeks 
FO treatment (100μl/animal/day). Distinction between microglial cells and 
macrophages was assessed using double immunostaining with anti-TMEM119 and 
anti-Iba1 antibodies respectively. Immunostaining was observed by confocal 
microscopy. For western blot analysis anti-TREM-2 and anti-IDE were used to 
observe potential mechanism responsible for extracellular clearance of toxic Aβ 
forms. Quantification was done by Image Quant software. Our results showed that 
short-term FO supplementation affects the localization and number of microglial cells 
and macrophages. Macrophages were located around the plaque and were responsible 
for the formation of a mechanical barrier, while microglial cells showed an increased 
number under the treatment and were located far from the plaques. Furthermore, the 
treatment did not seem to affect the level of IDE, while on the other hand it 
significantly increased the level of TREM-2 (ultimately sustaining the microglial 
response to Aβ-plaque-induced pathology).
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Short-term fish oil treatment increases number of microglial cells  and expression level of TREM-2 in parietal cortex of 5XFAD mice
SP  - 65
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5851
ER  - 

@conference{
author = "Jović, Milena and Simeunović, Valentina and Vukojević, Anđela and Prvulović, Milica and Sokanović, Srđan and Mladenović, Aleksandra and Milanović, Desanka and Todorović, Smilja and Lončarević-Vasiljković, Nataša",
year = "2023",
abstract = "According to the amyloid hypothesis of Alcheimer’s disease (AD), disruption of 
balance between production and clearance of Aβ from the cells leads to the 
progressive accumulation and aggregation of amyloid beta (Aβ) peptides in the brain. 
The glial system (microglial cells and astrocytes) is responsible for maintaining 
homeostasis in the brain which implies its important role in the development and 
progression of AD. Our previous work revealed that the short-term fish oil (FO) 
treatment in 5xFAD mice, (AD animal model), reduces toxic Aβ load and increases 
number of microglial/macrophage cells in parietal cortex. In the present study we 
aimed to further decipher the roles of microglial and macrophage cells and to 
elucidate possible mechanisms responsible for observed reduced level of toxic Aβ42 
peptide. For this purpose, western blot and immunohistochemical analysis were used 
to detect changes in parietal cortex of three-month-old 5xFAD mice after three weeks 
FO treatment (100μl/animal/day). Distinction between microglial cells and 
macrophages was assessed using double immunostaining with anti-TMEM119 and 
anti-Iba1 antibodies respectively. Immunostaining was observed by confocal 
microscopy. For western blot analysis anti-TREM-2 and anti-IDE were used to 
observe potential mechanism responsible for extracellular clearance of toxic Aβ 
forms. Quantification was done by Image Quant software. Our results showed that 
short-term FO supplementation affects the localization and number of microglial cells 
and macrophages. Macrophages were located around the plaque and were responsible 
for the formation of a mechanical barrier, while microglial cells showed an increased 
number under the treatment and were located far from the plaques. Furthermore, the 
treatment did not seem to affect the level of IDE, while on the other hand it 
significantly increased the level of TREM-2 (ultimately sustaining the microglial 
response to Aβ-plaque-induced pathology).",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Short-term fish oil treatment increases number of microglial cells  and expression level of TREM-2 in parietal cortex of 5XFAD mice",
pages = "65",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5851"
}

Jović, M., Simeunović, V., Vukojević, A., Prvulović, M., Sokanović, S., Mladenović, A., Milanović, D., Todorović, S.,& Lončarević-Vasiljković, N.. (2023). Short-term fish oil treatment increases number of microglial cells  and expression level of TREM-2 in parietal cortex of 5XFAD mice. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 65.
https://hdl.handle.net/21.15107/rcub_ibiss_5851

Jović M, Simeunović V, Vukojević A, Prvulović M, Sokanović S, Mladenović A, Milanović D, Todorović S, Lončarević-Vasiljković N. Short-term fish oil treatment increases number of microglial cells  and expression level of TREM-2 in parietal cortex of 5XFAD mice. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:65.
https://hdl.handle.net/21.15107/rcub_ibiss_5851 .

Jović, Milena, Simeunović, Valentina, Vukojević, Anđela, Prvulović, Milica, Sokanović, Srđan, Mladenović, Aleksandra, Milanović, Desanka, Todorović, Smilja, Lončarević-Vasiljković, Nataša, "Short-term fish oil treatment increases number of microglial cells  and expression level of TREM-2 in parietal cortex of 5XFAD mice" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):65,
https://hdl.handle.net/21.15107/rcub_ibiss_5851 .

TY  - CONF
AU  - Vukojević, Anđela
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
AU  - Sokanović, Srđan
AU  - Simeunović, Valentina
AU  - Jović, Milena
AU  - Milanović, Desanka
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5850
AB  - Systemic inflammation can be triggered by structural components of gut bacteria such 
as LPS, leading to a cascade of inflammatory pathways involving cytokines and other 
pro-inflammatory molecules. Dietary interventions have been shown to influence 
these pathways. Fermented food as a rich source of nutrients, phytochemicals and 
bioactive compounds, have the significant biological activities, such as anti inflammatory and immunomodulatory functions. In addition, some of these functions 
are due to the high content of lactic acid bacteria (LAB) and their products.
The aim of this study was to investigate the effects of sauerkraut brine (SB) on 
lipopolysaccharides (LPS)-induced central and peripheral inflammation in C57BL/6 
mice. Ninety postnatal day-old mice were divided into 3 groups: naive, treated with 
either 150 µl sauerkraut brine and pasteurized sauerkraut brine (PSB) by oral 
administration for 5 weeks. Control animals (CON) received an equivalent amount of 
saline. Both groups received LPS (0.5 mg/kg. i.p.) 3 hours before sacrifice. Brain and 
liver were isolated for PCR and Western blot analyzes.
The SB and PSB treatments did not affect body weight and behavior of mice 
compared with CON mice. At the molecular level, the sauerkraut brine affected the 
TLR4-MyD88 signaling pathway, resulting in a reduction of cytokines and other 
inflammatory molecules in mice cortex, which was not the case in the liver. Since 
analysis of sauerkraut revealed a high abundance of lactic acid bacteria (LAB) 
(1.8x106
/gr), future studies should clarify whether the anti-inflammatory effect of 
sauerkraut brine is mediated by the mouse microbiota.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Effect of sauerkraut brine in central and peripheral LPS-induced  inflammation in C57BL/6 mice
SP  - 68
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5850
ER  - 

@conference{
author = "Vukojević, Anđela and Prvulović, Milica and Todorović, Smilja and Mladenović, Aleksandra and Sokanović, Srđan and Simeunović, Valentina and Jović, Milena and Milanović, Desanka",
year = "2023",
abstract = "Systemic inflammation can be triggered by structural components of gut bacteria such 
as LPS, leading to a cascade of inflammatory pathways involving cytokines and other 
pro-inflammatory molecules. Dietary interventions have been shown to influence 
these pathways. Fermented food as a rich source of nutrients, phytochemicals and 
bioactive compounds, have the significant biological activities, such as anti inflammatory and immunomodulatory functions. In addition, some of these functions 
are due to the high content of lactic acid bacteria (LAB) and their products.
The aim of this study was to investigate the effects of sauerkraut brine (SB) on 
lipopolysaccharides (LPS)-induced central and peripheral inflammation in C57BL/6 
mice. Ninety postnatal day-old mice were divided into 3 groups: naive, treated with 
either 150 µl sauerkraut brine and pasteurized sauerkraut brine (PSB) by oral 
administration for 5 weeks. Control animals (CON) received an equivalent amount of 
saline. Both groups received LPS (0.5 mg/kg. i.p.) 3 hours before sacrifice. Brain and 
liver were isolated for PCR and Western blot analyzes.
The SB and PSB treatments did not affect body weight and behavior of mice 
compared with CON mice. At the molecular level, the sauerkraut brine affected the 
TLR4-MyD88 signaling pathway, resulting in a reduction of cytokines and other 
inflammatory molecules in mice cortex, which was not the case in the liver. Since 
analysis of sauerkraut revealed a high abundance of lactic acid bacteria (LAB) 
(1.8x106
/gr), future studies should clarify whether the anti-inflammatory effect of 
sauerkraut brine is mediated by the mouse microbiota.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Effect of sauerkraut brine in central and peripheral LPS-induced  inflammation in C57BL/6 mice",
pages = "68",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5850"
}

Vukojević, A., Prvulović, M., Todorović, S., Mladenović, A., Sokanović, S., Simeunović, V., Jović, M.,& Milanović, D.. (2023). Effect of sauerkraut brine in central and peripheral LPS-induced  inflammation in C57BL/6 mice. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 68.
https://hdl.handle.net/21.15107/rcub_ibiss_5850

Vukojević A, Prvulović M, Todorović S, Mladenović A, Sokanović S, Simeunović V, Jović M, Milanović D. Effect of sauerkraut brine in central and peripheral LPS-induced  inflammation in C57BL/6 mice. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:68.
https://hdl.handle.net/21.15107/rcub_ibiss_5850 .

Vukojević, Anđela, Prvulović, Milica, Todorović, Smilja, Mladenović, Aleksandra, Sokanović, Srđan, Simeunović, Valentina, Jović, Milena, Milanović, Desanka, "Effect of sauerkraut brine in central and peripheral LPS-induced  inflammation in C57BL/6 mice" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):68,
https://hdl.handle.net/21.15107/rcub_ibiss_5850 .

TY  - CONF
AU  - Sokanović, Srđan
AU  - Simeunović, Valentina
AU  - Todorović, Smilja
AU  - Milanović, Desanka
AU  - Prvulović, Milica
AU  - Jović, Milena
AU  - Vukojević, Anđela
AU  - Mladenović, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5853
AB  - Here we analyzed effect of long-term (18 months) caloric restriction (60% reduction 
in daily food intake) on pituitary-gonadal axis functionality during male rat aging. As 
it was expected, serum and testicular testosterone (T) levels were significantly 
reduced in intact 24-month-old rats comparing to 6-month-old controls. Decreased T 
synthesis and production was accompanied by decreased expression of Lhr, 
steroidogenic genes/protein (Star/StAR, Cyp11a1, Cyp17a1, Hsd3b1, Hsd17b3) and 
Insl3 expression. Pituitary expression profiles of Lhb, Fshb Cga, Gnrhr, Prl and Pomc 
were not changed during aging while Prlr showed significantly decreased expression 
level at the age of 24 months. Decrement in testosterone production was accompanied 
by increased serum levels of total cholesterol, LDL and triglycerides. Serum levels of 
HDL and VitaminD were not changed with aging. The caloric restriction additionally 
decreased T levels in the serum and testicular extracts of aged animals as well as the 
expression of the Star, Cyp11a1 and Ldlr in the testicular tissue without affecting 
expression profile of genes responsible for de novo synthesis of cholesterol (Npc1, 
Hmgcr, Cyp46, Screbf1, Soat1). At the same time we were able to detect elevated 
expression of Lhb and Fshb in the pituitary tissue. The treatment decreased levels of 
total cholesterol, triglycerides, VitaminD and elevated HDL. In line with the obtained 
results it is likely that primary hypogonadism has been presented in our model with 
the evidence that long-term caloric restriction has no beneficial effects on testosterone 
homeostasis during rat aging.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Effects of long-term caloric restriction on pituitary-gonadal axis  functionality of aged male Wistar rats
SP  - 73
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5853
ER  - 

@conference{
author = "Sokanović, Srđan and Simeunović, Valentina and Todorović, Smilja and Milanović, Desanka and Prvulović, Milica and Jović, Milena and Vukojević, Anđela and Mladenović, Aleksandra",
year = "2023",
abstract = "Here we analyzed effect of long-term (18 months) caloric restriction (60% reduction 
in daily food intake) on pituitary-gonadal axis functionality during male rat aging. As 
it was expected, serum and testicular testosterone (T) levels were significantly 
reduced in intact 24-month-old rats comparing to 6-month-old controls. Decreased T 
synthesis and production was accompanied by decreased expression of Lhr, 
steroidogenic genes/protein (Star/StAR, Cyp11a1, Cyp17a1, Hsd3b1, Hsd17b3) and 
Insl3 expression. Pituitary expression profiles of Lhb, Fshb Cga, Gnrhr, Prl and Pomc 
were not changed during aging while Prlr showed significantly decreased expression 
level at the age of 24 months. Decrement in testosterone production was accompanied 
by increased serum levels of total cholesterol, LDL and triglycerides. Serum levels of 
HDL and VitaminD were not changed with aging. The caloric restriction additionally 
decreased T levels in the serum and testicular extracts of aged animals as well as the 
expression of the Star, Cyp11a1 and Ldlr in the testicular tissue without affecting 
expression profile of genes responsible for de novo synthesis of cholesterol (Npc1, 
Hmgcr, Cyp46, Screbf1, Soat1). At the same time we were able to detect elevated 
expression of Lhb and Fshb in the pituitary tissue. The treatment decreased levels of 
total cholesterol, triglycerides, VitaminD and elevated HDL. In line with the obtained 
results it is likely that primary hypogonadism has been presented in our model with 
the evidence that long-term caloric restriction has no beneficial effects on testosterone 
homeostasis during rat aging.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Effects of long-term caloric restriction on pituitary-gonadal axis  functionality of aged male Wistar rats",
pages = "73",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5853"
}

Sokanović, S., Simeunović, V., Todorović, S., Milanović, D., Prvulović, M., Jović, M., Vukojević, A.,& Mladenović, A.. (2023). Effects of long-term caloric restriction on pituitary-gonadal axis  functionality of aged male Wistar rats. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 73.
https://hdl.handle.net/21.15107/rcub_ibiss_5853

Sokanović S, Simeunović V, Todorović S, Milanović D, Prvulović M, Jović M, Vukojević A, Mladenović A. Effects of long-term caloric restriction on pituitary-gonadal axis  functionality of aged male Wistar rats. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:73.
https://hdl.handle.net/21.15107/rcub_ibiss_5853 .

Sokanović, Srđan, Simeunović, Valentina, Todorović, Smilja, Milanović, Desanka, Prvulović, Milica, Jović, Milena, Vukojević, Anđela, Mladenović, Aleksandra, "Effects of long-term caloric restriction on pituitary-gonadal axis  functionality of aged male Wistar rats" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):73,
https://hdl.handle.net/21.15107/rcub_ibiss_5853 .

TY  - CONF
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Simeunović, Valentina
AU  - Vukojević, Anđela
AU  - Sokanović, Srđan
AU  - Jović, Milena
AU  - Milanović, Desanka
AU  - Mladenović, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5840
AB  - Caloric restriction (CR) is widely known for delaying age-related changes, but its 
duration and onset can significantly alter its protective potential. One of the 
underlying mechanisms of the effect of CR on aging is considered to be mTOR 
pathway, an important player in nutrient sensing and regulation of cellular 
metabolism.
Adult, middle-aged, and old male Wistar rats were exposed to CR (60% of AL) to 
study the effect of CR of early (EOCR) and late onset (LOCR). Ad libitum (AL) fed 
animals were used to test the effects of aging and as age-matched controls for the 
effect of CR. Western blot was used to analyze the expression of proteins involved in 
the signaling cascade of mTOR complex 1 (mTORC1) in rat hippocampus. 
At 18 months of age, EOCR led to a decrease in phosphorylation of mTOR S2448, 
whereas LOCR led to its increase at 24 months of age. pAkt T308 was decreased with 
LOCR at 18 months, while at 24 months EOCR and LOCR increased its 
phosphorylation. LOCR also led to an increased phosphorylation of p70S6K1 at 24 
months of age. 
Although EOCR led to a decrease in phosphorylation of mTOR at 18 months of age, 
this effect was lost at 24 months, and was also not affecting the activation of the two 
kinases targeting mTOR S2448. Negative effect of short-term LOCR at 24 months 
was consistent in all examined proteins suggesting a caution when implementing CR 
later in life.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - MTORC1 signaling pathway changes under the effect of caloric  restriction in the hippocampus of male Wistar rats
SP  - 74
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5840
ER  - 

@conference{
author = "Prvulović, Milica and Todorović, Smilja and Simeunović, Valentina and Vukojević, Anđela and Sokanović, Srđan and Jović, Milena and Milanović, Desanka and Mladenović, Aleksandra",
year = "2023",
abstract = "Caloric restriction (CR) is widely known for delaying age-related changes, but its 
duration and onset can significantly alter its protective potential. One of the 
underlying mechanisms of the effect of CR on aging is considered to be mTOR 
pathway, an important player in nutrient sensing and regulation of cellular 
metabolism.
Adult, middle-aged, and old male Wistar rats were exposed to CR (60% of AL) to 
study the effect of CR of early (EOCR) and late onset (LOCR). Ad libitum (AL) fed 
animals were used to test the effects of aging and as age-matched controls for the 
effect of CR. Western blot was used to analyze the expression of proteins involved in 
the signaling cascade of mTOR complex 1 (mTORC1) in rat hippocampus. 
At 18 months of age, EOCR led to a decrease in phosphorylation of mTOR S2448, 
whereas LOCR led to its increase at 24 months of age. pAkt T308 was decreased with 
LOCR at 18 months, while at 24 months EOCR and LOCR increased its 
phosphorylation. LOCR also led to an increased phosphorylation of p70S6K1 at 24 
months of age. 
Although EOCR led to a decrease in phosphorylation of mTOR at 18 months of age, 
this effect was lost at 24 months, and was also not affecting the activation of the two 
kinases targeting mTOR S2448. Negative effect of short-term LOCR at 24 months 
was consistent in all examined proteins suggesting a caution when implementing CR 
later in life.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "MTORC1 signaling pathway changes under the effect of caloric  restriction in the hippocampus of male Wistar rats",
pages = "74",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5840"
}

Prvulović, M., Todorović, S., Simeunović, V., Vukojević, A., Sokanović, S., Jović, M., Milanović, D.,& Mladenović, A.. (2023). MTORC1 signaling pathway changes under the effect of caloric  restriction in the hippocampus of male Wistar rats. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 74.
https://hdl.handle.net/21.15107/rcub_ibiss_5840

Prvulović M, Todorović S, Simeunović V, Vukojević A, Sokanović S, Jović M, Milanović D, Mladenović A. MTORC1 signaling pathway changes under the effect of caloric  restriction in the hippocampus of male Wistar rats. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:74.
https://hdl.handle.net/21.15107/rcub_ibiss_5840 .

Prvulović, Milica, Todorović, Smilja, Simeunović, Valentina, Vukojević, Anđela, Sokanović, Srđan, Jović, Milena, Milanović, Desanka, Mladenović, Aleksandra, "MTORC1 signaling pathway changes under the effect of caloric  restriction in the hippocampus of male Wistar rats" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):74,
https://hdl.handle.net/21.15107/rcub_ibiss_5840 .

TY  - JOUR
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Milanović, Desanka
AU  - Jović, Milena
AU  - Vujović, Predrag
AU  - Kanazir, Selma
AU  - Mladenović, Aleksandra
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5303
AB  - Although initially recognized as a universally beneficial approach for the prevention of age-related impairments, the outcome of calorie restriction (CR) is now known to depend on several factors, most notably the age of the subject at the CR commencement, and CR duration. We aimed to examine if and how CR affects anxiety-like behaviour when it is introduced at middle age and late middle age. In addition, as the dopaminergic system is one of the main neurotransmitter systems involved in controlling anxiety, we examined the expression of dopamine receptors (D1R, D2R) in the cortex, striatum, and mesencephalon of male Wistar rats of varying ages. The study was performed on rats fed ad libitum (AL) or exposed to calorie restriction (60% of AL intake). Open field and light-dark tests were used to study anxiety-like behaviour, while PCR and Western blot were used to examine the expression of dopamine receptors. Calorie restriction implemented at middle-age led to variable outcomes on anxiety-like behaviour, while CR implemented at late middle age increased anxiety and decreased the availability of D2R levels in the cortex and mesencephalon. Taken together, these results advise caution when implementing calorie restriction late in life. © 2022
PB  - Elsevier Ireland Ltd
T2  - Mechanisms of Ageing and Development
T1  - Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner
VL  - 204
DO  - 10.1016/j.mad.2022.111666
SP  - 111666
ER  - 

@article{
author = "Prvulović, Milica and Todorović, Smilja and Milanović, Desanka and Jović, Milena and Vujović, Predrag and Kanazir, Selma and Mladenović, Aleksandra",
year = "2022",
abstract = "Although initially recognized as a universally beneficial approach for the prevention of age-related impairments, the outcome of calorie restriction (CR) is now known to depend on several factors, most notably the age of the subject at the CR commencement, and CR duration. We aimed to examine if and how CR affects anxiety-like behaviour when it is introduced at middle age and late middle age. In addition, as the dopaminergic system is one of the main neurotransmitter systems involved in controlling anxiety, we examined the expression of dopamine receptors (D1R, D2R) in the cortex, striatum, and mesencephalon of male Wistar rats of varying ages. The study was performed on rats fed ad libitum (AL) or exposed to calorie restriction (60% of AL intake). Open field and light-dark tests were used to study anxiety-like behaviour, while PCR and Western blot were used to examine the expression of dopamine receptors. Calorie restriction implemented at middle-age led to variable outcomes on anxiety-like behaviour, while CR implemented at late middle age increased anxiety and decreased the availability of D2R levels in the cortex and mesencephalon. Taken together, these results advise caution when implementing calorie restriction late in life. © 2022",
publisher = "Elsevier Ireland Ltd",
journal = "Mechanisms of Ageing and Development",
title = "Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner",
volume = "204",
doi = "10.1016/j.mad.2022.111666",
pages = "111666"
}

Prvulović, M., Todorović, S., Milanović, D., Jović, M., Vujović, P., Kanazir, S.,& Mladenović, A.. (2022). Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner. in Mechanisms of Ageing and Development
Elsevier Ireland Ltd., 204, 111666.
https://doi.org/10.1016/j.mad.2022.111666

Prvulović M, Todorović S, Milanović D, Jović M, Vujović P, Kanazir S, Mladenović A. Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner. in Mechanisms of Ageing and Development. 2022;204:111666.
doi:10.1016/j.mad.2022.111666 .

Prvulović, Milica, Todorović, Smilja, Milanović, Desanka, Jović, Milena, Vujović, Predrag, Kanazir, Selma, Mladenović, Aleksandra, "Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner" in Mechanisms of Ageing and Development, 204 (2022):111666,
https://doi.org/10.1016/j.mad.2022.111666 . .

TY  - JOUR
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Milanović, Desanka
AU  - Jović, Milena
AU  - Vujović, Predrag
AU  - Kanazir, Selma
AU  - Mladenović, Aleksandra
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0047637422000483
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4946
AB  - Although initially recognized as a universally beneficial approach for the prevention of age-related impairments, the outcome of calorie restriction (CR) is now known to depend on several factors, most notably the age of the subject at the CR commencement, and CR duration. We aimed to examine if and how CR affects anxiety-like behaviour when it is introduced at middle age and late middle age. In addition, as the dopaminergic system is one of the main neurotransmitter systems involved in controlling anxiety, we examined the expression of dopamine receptors (D1R, D2R) in the cortex, striatum, and mesencephalon of male Wistar rats of varying ages. The study was performed on rats fed ad libitum (AL) or exposed to calorie restriction (60% of AL intake). Open field and light-dark tests were used to study anxiety-like behaviour, while PCR and Western blot were used to examine the expression of dopamine receptors. Calorie restriction implemented at middle-age led to variable outcomes on anxiety-like behaviour, while CR implemented at late middle age increased anxiety and decreased the availability of D2R levels in the cortex and mesencephalon. Taken together, these results advise caution when implementing calorie restriction late in life.
PB  - Elsevier Ireland Ltd
T2  - Mechanisms of Ageing and Development
T1  - Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner.
VL  - 204
DO  - 10.1016/j.mad.2022.111666
SP  - 111666
ER  - 

@article{
author = "Prvulović, Milica and Todorović, Smilja and Milanović, Desanka and Jović, Milena and Vujović, Predrag and Kanazir, Selma and Mladenović, Aleksandra",
year = "2022",
abstract = "Although initially recognized as a universally beneficial approach for the prevention of age-related impairments, the outcome of calorie restriction (CR) is now known to depend on several factors, most notably the age of the subject at the CR commencement, and CR duration. We aimed to examine if and how CR affects anxiety-like behaviour when it is introduced at middle age and late middle age. In addition, as the dopaminergic system is one of the main neurotransmitter systems involved in controlling anxiety, we examined the expression of dopamine receptors (D1R, D2R) in the cortex, striatum, and mesencephalon of male Wistar rats of varying ages. The study was performed on rats fed ad libitum (AL) or exposed to calorie restriction (60% of AL intake). Open field and light-dark tests were used to study anxiety-like behaviour, while PCR and Western blot were used to examine the expression of dopamine receptors. Calorie restriction implemented at middle-age led to variable outcomes on anxiety-like behaviour, while CR implemented at late middle age increased anxiety and decreased the availability of D2R levels in the cortex and mesencephalon. Taken together, these results advise caution when implementing calorie restriction late in life.",
publisher = "Elsevier Ireland Ltd",
journal = "Mechanisms of Ageing and Development",
title = "Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner.",
volume = "204",
doi = "10.1016/j.mad.2022.111666",
pages = "111666"
}

Prvulović, M., Todorović, S., Milanović, D., Jović, M., Vujović, P., Kanazir, S.,& Mladenović, A.. (2022). Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner.. in Mechanisms of Ageing and Development
Elsevier Ireland Ltd., 204, 111666.
https://doi.org/10.1016/j.mad.2022.111666

Prvulović M, Todorović S, Milanović D, Jović M, Vujović P, Kanazir S, Mladenović A. Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner.. in Mechanisms of Ageing and Development. 2022;204:111666.
doi:10.1016/j.mad.2022.111666 .

Prvulović, Milica, Todorović, Smilja, Milanović, Desanka, Jović, Milena, Vujović, Predrag, Kanazir, Selma, Mladenović, Aleksandra, "Calorie restriction changes the anxiety-like behaviour of ageing male Wistar rats in an onset- and duration-dependent manner." in Mechanisms of Ageing and Development, 204 (2022):111666,
https://doi.org/10.1016/j.mad.2022.111666 . .

TY  - CONF
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Milanović, Desanka
AU  - Vukojević, Anđela
AU  - Simeunović, Valentina
AU  - Jović, Milena
AU  - Mladenović, Aleksandra
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5798
AB  - Calorie restriction (CR) is known to prolong lifespan and healthspan, - life period free of age-related diseases. However, generality of CR’s beneficial effect is being questioned recently. Few studies showed that the outcome of CR could vary depending on its onset and duration. Herein, we examined and compared potential of different CR paradigms to modulate anxiety-like behavior. Methods: Ad libitum (AL) fed animals were used as controls. Female Wistar rats of different age (adult, middle-aged and aged) were exposed to CR (60% of AL), to examine the effect of early-onset CR (EOCR) and late-onset CR (LOCR). Open field (OF) and Light-dark box (LDB) test were used for anxiety assessment. Results: Aged 
LOCR animals had decreased number of entries and time spent in the central area of the OF. LDB test results, however, implied a protective effect of EOCR since both middle-aged and aged EOCR animals showed increased number of entries in the light compartment and spent more time in the door area or in the light compartment. LOCR had different effect depending on animals’ age at the CR onset. Conclusions: EOCR ameliorates anxiety-like behavior and this effect seems to persevere till 
old age. Implementing CR later in life should be taken with caution, since its’ effect could vary from protective to detrimental, depending on the onset. Additionally, different results were obtained using OF and LDB, suggesting that more than one test should be used to provide proper insight in certain behavioral changes.
PB  - Federation of European Neuroscience Societies
C3  - E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France
T1  - Early-onset and late-onset calorie restriction differently modulate anxiety-like bahavior in aging female Wistar rats
SP  - S07-100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5798
ER  - 

@conference{
author = "Prvulović, Milica and Todorović, Smilja and Milanović, Desanka and Vukojević, Anđela and Simeunović, Valentina and Jović, Milena and Mladenović, Aleksandra",
year = "2022",
abstract = "Calorie restriction (CR) is known to prolong lifespan and healthspan, - life period free of age-related diseases. However, generality of CR’s beneficial effect is being questioned recently. Few studies showed that the outcome of CR could vary depending on its onset and duration. Herein, we examined and compared potential of different CR paradigms to modulate anxiety-like behavior. Methods: Ad libitum (AL) fed animals were used as controls. Female Wistar rats of different age (adult, middle-aged and aged) were exposed to CR (60% of AL), to examine the effect of early-onset CR (EOCR) and late-onset CR (LOCR). Open field (OF) and Light-dark box (LDB) test were used for anxiety assessment. Results: Aged 
LOCR animals had decreased number of entries and time spent in the central area of the OF. LDB test results, however, implied a protective effect of EOCR since both middle-aged and aged EOCR animals showed increased number of entries in the light compartment and spent more time in the door area or in the light compartment. LOCR had different effect depending on animals’ age at the CR onset. Conclusions: EOCR ameliorates anxiety-like behavior and this effect seems to persevere till 
old age. Implementing CR later in life should be taken with caution, since its’ effect could vary from protective to detrimental, depending on the onset. Additionally, different results were obtained using OF and LDB, suggesting that more than one test should be used to provide proper insight in certain behavioral changes.",
publisher = "Federation of European Neuroscience Societies",
journal = "E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France",
title = "Early-onset and late-onset calorie restriction differently modulate anxiety-like bahavior in aging female Wistar rats",
pages = "S07-100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5798"
}

Prvulović, M., Todorović, S., Milanović, D., Vukojević, A., Simeunović, V., Jović, M.,& Mladenović, A.. (2022). Early-onset and late-onset calorie restriction differently modulate anxiety-like bahavior in aging female Wistar rats. in E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France
Federation of European Neuroscience Societies., S07-100.
https://hdl.handle.net/21.15107/rcub_ibiss_5798

Prvulović M, Todorović S, Milanović D, Vukojević A, Simeunović V, Jović M, Mladenović A. Early-onset and late-onset calorie restriction differently modulate anxiety-like bahavior in aging female Wistar rats. in E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France. 2022;:S07-100.
https://hdl.handle.net/21.15107/rcub_ibiss_5798 .

Prvulović, Milica, Todorović, Smilja, Milanović, Desanka, Vukojević, Anđela, Simeunović, Valentina, Jović, Milena, Mladenović, Aleksandra, "Early-onset and late-onset calorie restriction differently modulate anxiety-like bahavior in aging female Wistar rats" in E-book of Abstracts: FENS Forum 2022; 2022 Jul 9-13; Paris, France (2022):S07-100,
https://hdl.handle.net/21.15107/rcub_ibiss_5798 .

TY  - CONF
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
AU  - Prvulović, Milica
AU  - Milanović, Desanka
AU  - Simeunović, Valentina
AU  - Jović, Milena
AU  - Sokanović, Srđan
AU  - Vukojević, Anđela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5381
AB  - Aging is an inevitable, complex and dynamic process of natural change, leading to deleterious age­related modifications. Still, the aging process can be modified by
lifestyle interventions, like dietary restriction (DR). Although DR is a proven experimental paradigm for lifespan and healthspan extension, the impact of the type, onset
and duration of DR is still debatable. In order to test different dietary types, we used frailty as a tool for detecting DR outcomes throughout aging. In this report, we
describe that different dietary protocols have various impact on age­related behavioral parameters and frailty status.
We exposed male Wistar rats of various age to ad libitum (AL) or DR (60% of AL daily intake) feeding regimens with different onsets. The effect of DR on locomotor
activity, memory and learning was examined in 12­, 18­ and 24­month­old animals using open field (OF) and Y maze test. We used behavioral data to create unique
frailty score (FS) and determine frailty status in those animals. 
Our results indicated that various durations and onsets of DR can alter the course of aging, with the life­long DR responsible for the most profound effect. Shorter
duration/later onset of DR had minor or in some cases even detrimental impact on behavior and frailty during aging.
PB  - Federation of European Biochemical Societies
C3  - Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
T1  - Path to healthy aging: assessment of different dietary restriction protocols through behavioral and frailty measurements
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5381
ER  - 

@conference{
author = "Todorović, Smilja and Mladenović, Aleksandra and Prvulović, Milica and Milanović, Desanka and Simeunović, Valentina and Jović, Milena and Sokanović, Srđan and Vukojević, Anđela",
year = "2022",
abstract = "Aging is an inevitable, complex and dynamic process of natural change, leading to deleterious age­related modifications. Still, the aging process can be modified by
lifestyle interventions, like dietary restriction (DR). Although DR is a proven experimental paradigm for lifespan and healthspan extension, the impact of the type, onset
and duration of DR is still debatable. In order to test different dietary types, we used frailty as a tool for detecting DR outcomes throughout aging. In this report, we
describe that different dietary protocols have various impact on age­related behavioral parameters and frailty status.
We exposed male Wistar rats of various age to ad libitum (AL) or DR (60% of AL daily intake) feeding regimens with different onsets. The effect of DR on locomotor
activity, memory and learning was examined in 12­, 18­ and 24­month­old animals using open field (OF) and Y maze test. We used behavioral data to create unique
frailty score (FS) and determine frailty status in those animals. 
Our results indicated that various durations and onsets of DR can alter the course of aging, with the life­long DR responsible for the most profound effect. Shorter
duration/later onset of DR had minor or in some cases even detrimental impact on behavior and frailty during aging.",
publisher = "Federation of European Biochemical Societies",
journal = "Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece",
title = "Path to healthy aging: assessment of different dietary restriction protocols through behavioral and frailty measurements",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5381"
}

Todorović, S., Mladenović, A., Prvulović, M., Milanović, D., Simeunović, V., Jović, M., Sokanović, S.,& Vukojević, A.. (2022). Path to healthy aging: assessment of different dietary restriction protocols through behavioral and frailty measurements. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
Federation of European Biochemical Societies..
https://hdl.handle.net/21.15107/rcub_ibiss_5381

Todorović S, Mladenović A, Prvulović M, Milanović D, Simeunović V, Jović M, Sokanović S, Vukojević A. Path to healthy aging: assessment of different dietary restriction protocols through behavioral and frailty measurements. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5381 .

Todorović, Smilja, Mladenović, Aleksandra, Prvulović, Milica, Milanović, Desanka, Simeunović, Valentina, Jović, Milena, Sokanović, Srđan, Vukojević, Anđela, "Path to healthy aging: assessment of different dietary restriction protocols through behavioral and frailty measurements" in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5381 .

TY  - CONF
AU  - Simeunović, Valentina
AU  - Mladenović, Aleksandra
AU  - Milanović, Desanka
AU  - Prvulović, Milica
AU  - Jović, Milena
AU  - Sokanović, Srđan
AU  - Todorović, Smilja
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5321
AB  - It has been shown that insulin has an important role in many processes in the brain, like upholding the nutritional homeostasis in the hypothalamus and synaptic plasticity
in the hippocampus. Insulin exerts its effects by acting through the insulin signaling pathway. During aging, chronic activation of this pathway can occur, leading to insulin
resistance, which is in the basis of many neurodegenerative diseases. Numerous environmental factors, such as dietary restriction (DR), can postpone and / or slow
down many of the age­related processes. It is assumed that DR exerts its effect on insulin resistance through the insulin signaling pathway.
In this experiment we studied the effect of 40% DR (60% of ad libitum daily intake) on the expression of insulin, as well as on the amount of total (IRβ) and active
(pIRβ) form of insulin receptor in the hippocampus of male Wistar rats. We examined the effect of three different types of DR: DR1, which started at 6 months of age
and lasted up to 18 and 24 months, DR2, which lasted 6 months (12­18 months and 18­24 months of age), and DR3, which lasted 3 months (15­18 months and 21­24
months of age).
Our results showed that long­term DR1 led to a decrease in activity of insulin signaling pathway in the hippocampus of both 18­ and 24­month­old male Wistar rats,
which can further play a role in the prevention of neurodegenerative diseases.
PB  - Federation of European Biochemical Societies
C3  - Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
T1  - The effect of the duration of dietary restriction on insulin signaling pathway in the hippocampus of male Wistar rats
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5321
ER  - 

@conference{
author = "Simeunović, Valentina and Mladenović, Aleksandra and Milanović, Desanka and Prvulović, Milica and Jović, Milena and Sokanović, Srđan and Todorović, Smilja",
year = "2022",
abstract = "It has been shown that insulin has an important role in many processes in the brain, like upholding the nutritional homeostasis in the hypothalamus and synaptic plasticity
in the hippocampus. Insulin exerts its effects by acting through the insulin signaling pathway. During aging, chronic activation of this pathway can occur, leading to insulin
resistance, which is in the basis of many neurodegenerative diseases. Numerous environmental factors, such as dietary restriction (DR), can postpone and / or slow
down many of the age­related processes. It is assumed that DR exerts its effect on insulin resistance through the insulin signaling pathway.
In this experiment we studied the effect of 40% DR (60% of ad libitum daily intake) on the expression of insulin, as well as on the amount of total (IRβ) and active
(pIRβ) form of insulin receptor in the hippocampus of male Wistar rats. We examined the effect of three different types of DR: DR1, which started at 6 months of age
and lasted up to 18 and 24 months, DR2, which lasted 6 months (12­18 months and 18­24 months of age), and DR3, which lasted 3 months (15­18 months and 21­24
months of age).
Our results showed that long­term DR1 led to a decrease in activity of insulin signaling pathway in the hippocampus of both 18­ and 24­month­old male Wistar rats,
which can further play a role in the prevention of neurodegenerative diseases.",
publisher = "Federation of European Biochemical Societies",
journal = "Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece",
title = "The effect of the duration of dietary restriction on insulin signaling pathway in the hippocampus of male Wistar rats",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5321"
}

Simeunović, V., Mladenović, A., Milanović, D., Prvulović, M., Jović, M., Sokanović, S.,& Todorović, S.. (2022). The effect of the duration of dietary restriction on insulin signaling pathway in the hippocampus of male Wistar rats. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
Federation of European Biochemical Societies..
https://hdl.handle.net/21.15107/rcub_ibiss_5321

Simeunović V, Mladenović A, Milanović D, Prvulović M, Jović M, Sokanović S, Todorović S. The effect of the duration of dietary restriction on insulin signaling pathway in the hippocampus of male Wistar rats. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5321 .

Simeunović, Valentina, Mladenović, Aleksandra, Milanović, Desanka, Prvulović, Milica, Jović, Milena, Sokanović, Srđan, Todorović, Smilja, "The effect of the duration of dietary restriction on insulin signaling pathway in the hippocampus of male Wistar rats" in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5321 .

TY  - CONF
AU  - Vukojević, Anđela
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
AU  - Jović, Milena
AU  - Jovanović Macura, Irena
AU  - Perović, Milka
AU  - Milanović, Desanka
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5325
AB  - Non­transmittable chronic diseases are largely driven by chronic inflammation, which can be connected to poor diet and toxic products of commensal gut microbiome.
Diet intervention can influence gut microbiota function and composition. Fermented foods are specifically known to have anti­inflammatory and immunomodulatory
properties, attributed to their high antioxidant content and lactic acid­producing bacteria (LAB) 
In this study we examined the effects of sauerkraut brine (SB) on physiological and behavioral responses to systemic inflammation induced by lipopolysaccharides
(LPS) in a mouse model.  C57BL/6 mice 90 postnatal days old were used in this study. They were divided into 2 groups and treated with either 150 ml of sauerkraut
brine and pasteurized sauerkraut brine (PSB) for 5 weeks (via oral gavage). Control animals (CON) were receiving an equivalent amount of water. During the final
week of treatment, animals received 5 injections of LPS (0.5 mg/kg, i.p.). Behavior of animals was assessed before and after LPS administration, using the open field
test, light­dark box, Y­maze, tail­suspension and rota­rod test. Analysis of pro­inflammatory brain cytokines has been performed subsequently via Western blot and
PCR. Food consumption and body weight were measured throughout the experiment.
SB and PSB treatments did not influence body weights and behavior compared to CON mice. LPS treatment led to the weight loss and decreased food intake in all
experimental groups. The fastest recovery and a reduced inflammatory response was detected in the SB group. Behavioral analysis revealed differences between three
groups in responses to the LPS challenge.
PB  - Federation of European Biochemical Societies
C3  - Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
T1  - Protective role of fermented food in LPS-­induced inflammation in C57BL/6 mice
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5325
ER  - 

@conference{
author = "Vukojević, Anđela and Prvulović, Milica and Todorović, Smilja and Mladenović, Aleksandra and Jović, Milena and Jovanović Macura, Irena and Perović, Milka and Milanović, Desanka",
year = "2022",
abstract = "Non­transmittable chronic diseases are largely driven by chronic inflammation, which can be connected to poor diet and toxic products of commensal gut microbiome.
Diet intervention can influence gut microbiota function and composition. Fermented foods are specifically known to have anti­inflammatory and immunomodulatory
properties, attributed to their high antioxidant content and lactic acid­producing bacteria (LAB) 
In this study we examined the effects of sauerkraut brine (SB) on physiological and behavioral responses to systemic inflammation induced by lipopolysaccharides
(LPS) in a mouse model.  C57BL/6 mice 90 postnatal days old were used in this study. They were divided into 2 groups and treated with either 150 ml of sauerkraut
brine and pasteurized sauerkraut brine (PSB) for 5 weeks (via oral gavage). Control animals (CON) were receiving an equivalent amount of water. During the final
week of treatment, animals received 5 injections of LPS (0.5 mg/kg, i.p.). Behavior of animals was assessed before and after LPS administration, using the open field
test, light­dark box, Y­maze, tail­suspension and rota­rod test. Analysis of pro­inflammatory brain cytokines has been performed subsequently via Western blot and
PCR. Food consumption and body weight were measured throughout the experiment.
SB and PSB treatments did not influence body weights and behavior compared to CON mice. LPS treatment led to the weight loss and decreased food intake in all
experimental groups. The fastest recovery and a reduced inflammatory response was detected in the SB group. Behavioral analysis revealed differences between three
groups in responses to the LPS challenge.",
publisher = "Federation of European Biochemical Societies",
journal = "Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece",
title = "Protective role of fermented food in LPS-­induced inflammation in C57BL/6 mice",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5325"
}

Vukojević, A., Prvulović, M., Todorović, S., Mladenović, A., Jović, M., Jovanović Macura, I., Perović, M.,& Milanović, D.. (2022). Protective role of fermented food in LPS-­induced inflammation in C57BL/6 mice. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
Federation of European Biochemical Societies..
https://hdl.handle.net/21.15107/rcub_ibiss_5325

Vukojević A, Prvulović M, Todorović S, Mladenović A, Jović M, Jovanović Macura I, Perović M, Milanović D. Protective role of fermented food in LPS-­induced inflammation in C57BL/6 mice. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5325 .

Vukojević, Anđela, Prvulović, Milica, Todorović, Smilja, Mladenović, Aleksandra, Jović, Milena, Jovanović Macura, Irena, Perović, Milka, Milanović, Desanka, "Protective role of fermented food in LPS-­induced inflammation in C57BL/6 mice" in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5325 .

TY  - CONF
AU  - Jović, Milena
AU  - Mladenović, Aleksandra
AU  - Milanović, Desanka
AU  - Todorović, Smilja
AU  - Prvulović, Milica
AU  - Vukojević, Anđela
AU  - Simeunović, Valentina
AU  - Sokanović, Srđan
AU  - Lončarević, Nataša
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5323
AB  - The presence of large amounts of amyloid beta (Aβ) oligomers, amyloid plaques formation, and inflammation in the brain are one of the neuropathological characteristics
of Alzheimer's disease (AD). The use of supplements with omega­3 fatty acids has been associated with reduced risk and lessened AD pathology. The purpose of this
study was to elucidate whether such a treatment could affects glial cells and macrophages behavior in the early phase of the disease. 
We examined influence of fish oil (FO) treatment in 5xFAD mice, an animal model which rapidly recapitulates major hallmarks of AD amyloid pathology. Three­month
old female 5xFAD mice received FO (100μl/animal/day) via oral gavage during 3 weeks period. Histological analysis was used to detect changes in pathological
features of AD in parietal cortex of 5xFAD mice. Aβ peptide, macrophages, microglial cells and astrocytes were detected by anti­Aβ42­, anti­Iba­1, anti­TMEM119­
and anti­GFAP­antibody, respectively. Immunostaining was observed by confocal microscopy.  Quantification was done by ImageJ. FO supplementation alters the
behaviour of macrophages prompting them to establish a physical barrier around amyloid plaques and leads to changes in number of over all astrocytes and microglial
cells. 
These results confirmed and extended previous findings suggesting that FO supplementation suppresses brain aging and has a typical pleiotropic effect, suggesting that
FO in combination with other drugs could be good approach for long­term treatment in AD suppression.
PB  - Federation of European Biochemical Societies
C3  - Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
T1  - Short term fish oil supplementation changes glial cells function in 5XFAD mice
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5323
ER  - 

@conference{
author = "Jović, Milena and Mladenović, Aleksandra and Milanović, Desanka and Todorović, Smilja and Prvulović, Milica and Vukojević, Anđela and Simeunović, Valentina and Sokanović, Srđan and Lončarević, Nataša",
year = "2022",
abstract = "The presence of large amounts of amyloid beta (Aβ) oligomers, amyloid plaques formation, and inflammation in the brain are one of the neuropathological characteristics
of Alzheimer's disease (AD). The use of supplements with omega­3 fatty acids has been associated with reduced risk and lessened AD pathology. The purpose of this
study was to elucidate whether such a treatment could affects glial cells and macrophages behavior in the early phase of the disease. 
We examined influence of fish oil (FO) treatment in 5xFAD mice, an animal model which rapidly recapitulates major hallmarks of AD amyloid pathology. Three­month
old female 5xFAD mice received FO (100μl/animal/day) via oral gavage during 3 weeks period. Histological analysis was used to detect changes in pathological
features of AD in parietal cortex of 5xFAD mice. Aβ peptide, macrophages, microglial cells and astrocytes were detected by anti­Aβ42­, anti­Iba­1, anti­TMEM119­
and anti­GFAP­antibody, respectively. Immunostaining was observed by confocal microscopy.  Quantification was done by ImageJ. FO supplementation alters the
behaviour of macrophages prompting them to establish a physical barrier around amyloid plaques and leads to changes in number of over all astrocytes and microglial
cells. 
These results confirmed and extended previous findings suggesting that FO supplementation suppresses brain aging and has a typical pleiotropic effect, suggesting that
FO in combination with other drugs could be good approach for long­term treatment in AD suppression.",
publisher = "Federation of European Biochemical Societies",
journal = "Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece",
title = "Short term fish oil supplementation changes glial cells function in 5XFAD mice",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5323"
}

Jović, M., Mladenović, A., Milanović, D., Todorović, S., Prvulović, M., Vukojević, A., Simeunović, V., Sokanović, S.,& Lončarević, N.. (2022). Short term fish oil supplementation changes glial cells function in 5XFAD mice. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
Federation of European Biochemical Societies..
https://hdl.handle.net/21.15107/rcub_ibiss_5323

Jović M, Mladenović A, Milanović D, Todorović S, Prvulović M, Vukojević A, Simeunović V, Sokanović S, Lončarević N. Short term fish oil supplementation changes glial cells function in 5XFAD mice. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5323 .

Jović, Milena, Mladenović, Aleksandra, Milanović, Desanka, Todorović, Smilja, Prvulović, Milica, Vukojević, Anđela, Simeunović, Valentina, Sokanović, Srđan, Lončarević, Nataša, "Short term fish oil supplementation changes glial cells function in 5XFAD mice" in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5323 .

TY  - CONF
AU  - Mladenović, Aleksandra
AU  - Prvulović, Milica
AU  - Jović, Milena
AU  - Simeunović, Valentina
AU  - Sokanović, Srđan
AU  - Vukojević, Anđela
AU  - Todorović, Smilja
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5326
AB  - Frailty is a multidimensional syndrome in aging, allowing us the identification of the most vulnerable subset of older 
adults. In the past few decades, medium life expectancy is increased without an appropriate increase of healthspan. 
This phenomenon refers to an increased life expectancy without a proper increase of healthspan, the period of life 
during which the organism is healthy and free of serious disease. Since healthspan is declining, there are more 
individuals with morbidities and consequently an increasing number of frail individuals. When an individual is frail, 
even a minor complication can create a chain of events that can give a rise to a disability or even death. 
Nevertheless, there are old individuals who are not frail, so being old does not necessarily mean being frail. That is 
why the concept of frailty was created, to explain the heterogeneity in clinical outcomes between older patients, so it 
can be determined who is more likely to fall into the longevity trap.
The origin of frailty is based on the combination of genetic, biological, physical, psychological, social and 
environmental factors3
. It is important to keep in mind that frailty is a dynamic condition, and it is potentially 
reversible so the treatments, such as calorie restriction, can increase lifespan and concomitantly reduce age-related 
disease5
. Optimal aging would then depend on conditions that both promote long life and compress morbidity to 
achieve greater healthspan. Model organisms have been at the forefront in the aging research, giving us a wealth of 
information regarding different pathways to regulate aging. That is the reason why in the past decade, an effort was 
made to link the biology of aging with frailty in aging animal models. To achieve that, two major frailty models, 
“Fried frailty phenotype” and “Rockwood frailty index” have been adapted and validated in animals.
PB  - Federation of European Biochemical Societies
C3  - Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
T1  - Frailty: a way to measure aging
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5326
ER  - 

@conference{
author = "Mladenović, Aleksandra and Prvulović, Milica and Jović, Milena and Simeunović, Valentina and Sokanović, Srđan and Vukojević, Anđela and Todorović, Smilja",
year = "2022",
abstract = "Frailty is a multidimensional syndrome in aging, allowing us the identification of the most vulnerable subset of older 
adults. In the past few decades, medium life expectancy is increased without an appropriate increase of healthspan. 
This phenomenon refers to an increased life expectancy without a proper increase of healthspan, the period of life 
during which the organism is healthy and free of serious disease. Since healthspan is declining, there are more 
individuals with morbidities and consequently an increasing number of frail individuals. When an individual is frail, 
even a minor complication can create a chain of events that can give a rise to a disability or even death. 
Nevertheless, there are old individuals who are not frail, so being old does not necessarily mean being frail. That is 
why the concept of frailty was created, to explain the heterogeneity in clinical outcomes between older patients, so it 
can be determined who is more likely to fall into the longevity trap.
The origin of frailty is based on the combination of genetic, biological, physical, psychological, social and 
environmental factors3
. It is important to keep in mind that frailty is a dynamic condition, and it is potentially 
reversible so the treatments, such as calorie restriction, can increase lifespan and concomitantly reduce age-related 
disease5
. Optimal aging would then depend on conditions that both promote long life and compress morbidity to 
achieve greater healthspan. Model organisms have been at the forefront in the aging research, giving us a wealth of 
information regarding different pathways to regulate aging. That is the reason why in the past decade, an effort was 
made to link the biology of aging with frailty in aging animal models. To achieve that, two major frailty models, 
“Fried frailty phenotype” and “Rockwood frailty index” have been adapted and validated in animals.",
publisher = "Federation of European Biochemical Societies",
journal = "Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece",
title = "Frailty: a way to measure aging",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5326"
}

Mladenović, A., Prvulović, M., Jović, M., Simeunović, V., Sokanović, S., Vukojević, A.,& Todorović, S.. (2022). Frailty: a way to measure aging. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
Federation of European Biochemical Societies..
https://hdl.handle.net/21.15107/rcub_ibiss_5326

Mladenović A, Prvulović M, Jović M, Simeunović V, Sokanović S, Vukojević A, Todorović S. Frailty: a way to measure aging. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5326 .

Mladenović, Aleksandra, Prvulović, Milica, Jović, Milena, Simeunović, Valentina, Sokanović, Srđan, Vukojević, Anđela, Todorović, Smilja, "Frailty: a way to measure aging" in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5326 .

TY  - CONF
AU  - Todorović, Smilja
AU  - Prvulović, Milica
AU  - Milanović, Desanka
AU  - Sokanović, Srđan
AU  - Vukojević, Anđela
AU  - Simeunović, Valentina
AU  - Kanazir, Selma
AU  - Mladenović, Aleksandra
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5322
AB  - Dietary restriction (DR) is the oldest and the most investigated anti­aging intervention. Since the famous McCay's study that showed that the restriction of calories
without malnutrition prolongs mean and maximal lifespan in rats, thousands of papers demonstrated numerous beneficial effects of DR. DR is most famous for its proven
capability to prolong life span, but what we know today is that DR prevents age­related diabetes, it decreases both incidence and progression of the different forms of
cancer, protects from cardiovascular diseases, delays osteoporosis and sarcopenia. Its effects on the nervous system include preserved cognition, delayed brain atrophy,
and protection from various neurodegenerative diseases. 
By applying long­term dietary restrictions from the adulthood of male and female Wistar rats we demonstrated several beneficial outcomes. DR increased the level of
synaptic plasticity markers and neurotrophic factors in the rat cortex and hippocampus and preserved brain cholesterol homeostasis during aging. It also suppressed
apoptotic cell deaths after cortical injury and restored age­related impaired glucocorticoid receptor (GR) signalling in the brain. DR changed the expression of genes
involved in AD pathology and suppressed microglial activation following cortical injury. However, recently we have been shown that the outcome of DR is highly
dependent on the onset and duration. Namely, we demonstrated that short–term DR with a late­onset could have unfavorable effects on cognitive performances, anxiety
level, and frailty in Wistar rats. In addition, DR could have a negative impact when introduced to transgenic AD animals. The results of our studies impose great caution
when introducing CR to humans. To achieve its favorable effect DR should be introduced in humans up to the middle age.
PB  - Federation of European Biochemical Societies
C3  - Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
T1  - Dietary restriction as an antiaging intervention
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5322
ER  - 

@conference{
author = "Todorović, Smilja and Prvulović, Milica and Milanović, Desanka and Sokanović, Srđan and Vukojević, Anđela and Simeunović, Valentina and Kanazir, Selma and Mladenović, Aleksandra",
year = "2022",
abstract = "Dietary restriction (DR) is the oldest and the most investigated anti­aging intervention. Since the famous McCay's study that showed that the restriction of calories
without malnutrition prolongs mean and maximal lifespan in rats, thousands of papers demonstrated numerous beneficial effects of DR. DR is most famous for its proven
capability to prolong life span, but what we know today is that DR prevents age­related diabetes, it decreases both incidence and progression of the different forms of
cancer, protects from cardiovascular diseases, delays osteoporosis and sarcopenia. Its effects on the nervous system include preserved cognition, delayed brain atrophy,
and protection from various neurodegenerative diseases. 
By applying long­term dietary restrictions from the adulthood of male and female Wistar rats we demonstrated several beneficial outcomes. DR increased the level of
synaptic plasticity markers and neurotrophic factors in the rat cortex and hippocampus and preserved brain cholesterol homeostasis during aging. It also suppressed
apoptotic cell deaths after cortical injury and restored age­related impaired glucocorticoid receptor (GR) signalling in the brain. DR changed the expression of genes
involved in AD pathology and suppressed microglial activation following cortical injury. However, recently we have been shown that the outcome of DR is highly
dependent on the onset and duration. Namely, we demonstrated that short–term DR with a late­onset could have unfavorable effects on cognitive performances, anxiety
level, and frailty in Wistar rats. In addition, DR could have a negative impact when introduced to transgenic AD animals. The results of our studies impose great caution
when introducing CR to humans. To achieve its favorable effect DR should be introduced in humans up to the middle age.",
publisher = "Federation of European Biochemical Societies",
journal = "Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece",
title = "Dietary restriction as an antiaging intervention",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5322"
}

Todorović, S., Prvulović, M., Milanović, D., Sokanović, S., Vukojević, A., Simeunović, V., Kanazir, S.,& Mladenović, A.. (2022). Dietary restriction as an antiaging intervention. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
Federation of European Biochemical Societies..
https://hdl.handle.net/21.15107/rcub_ibiss_5322

Todorović S, Prvulović M, Milanović D, Sokanović S, Vukojević A, Simeunović V, Kanazir S, Mladenović A. Dietary restriction as an antiaging intervention. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5322 .

Todorović, Smilja, Prvulović, Milica, Milanović, Desanka, Sokanović, Srđan, Vukojević, Anđela, Simeunović, Valentina, Kanazir, Selma, Mladenović, Aleksandra, "Dietary restriction as an antiaging intervention" in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5322 .

TY  - CONF
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Milanović, Desanka
AU  - Vukojević, Anđela
AU  - Simeunović, Valentina
AU  - Jović, Milena
AU  - Sokanović, Srđan
AU  - Mladenović, Aleksandra
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5324
AB  - Calorie restriction (CR) is known as a potent intervention to prolong lifespan and healthspan. However, in recent studies it was shown that its effect is not universally
beneficial, but it can vary from protective to detrimental depending on age when implemented and its duration. Herein, we tried to examine the effect of CR on short­term 
and long­term memory. 
Ad libitum (AL) fed animals were used as controls. Wistar rats of different age (adult, middle­aged and aged) were exposed to CR (60% of AL), to examine
the effect of early­onset CR (EOCR) and late­onset CR (LOCR). Novel object recognition test (NORT) was used to assess short­term (STM) and long­term memory
(LTM) performance. 
Different pattern of changes was observed in males and females. While preserved memory was only measured in young AL males, in females both EOCR and LOCR
managed to preserve STM till 18 months of age, while LTM was preserved only with EOCR. In 24­month­old females LOCR failed to preserve memory and even
worsened STM and LTM performance in comparison to the age matching AL controls, while in males neither EO­ nor LOCR had effect on memory performance. 
EOCR succeeded to preserve STM and LTM in females, but till certain point in life. LOCR however seemed to have diametrically different effect depending on whether 
it was implemented at middle age or old age. Memory performance of male rats in NORT seems to be insensitive to CR treatments, since only young animals had ability 
to discriminate novel from old object.
PB  - Federation of European Biochemical Societies
C3  - Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
T1  - Calorie restriction changes long-term and short-term memory in rats in an  onset-, duration- and sex-dependent manner
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5324
ER  - 

@conference{
author = "Prvulović, Milica and Todorović, Smilja and Milanović, Desanka and Vukojević, Anđela and Simeunović, Valentina and Jović, Milena and Sokanović, Srđan and Mladenović, Aleksandra",
year = "2022",
abstract = "Calorie restriction (CR) is known as a potent intervention to prolong lifespan and healthspan. However, in recent studies it was shown that its effect is not universally
beneficial, but it can vary from protective to detrimental depending on age when implemented and its duration. Herein, we tried to examine the effect of CR on short­term 
and long­term memory. 
Ad libitum (AL) fed animals were used as controls. Wistar rats of different age (adult, middle­aged and aged) were exposed to CR (60% of AL), to examine
the effect of early­onset CR (EOCR) and late­onset CR (LOCR). Novel object recognition test (NORT) was used to assess short­term (STM) and long­term memory
(LTM) performance. 
Different pattern of changes was observed in males and females. While preserved memory was only measured in young AL males, in females both EOCR and LOCR
managed to preserve STM till 18 months of age, while LTM was preserved only with EOCR. In 24­month­old females LOCR failed to preserve memory and even
worsened STM and LTM performance in comparison to the age matching AL controls, while in males neither EO­ nor LOCR had effect on memory performance. 
EOCR succeeded to preserve STM and LTM in females, but till certain point in life. LOCR however seemed to have diametrically different effect depending on whether 
it was implemented at middle age or old age. Memory performance of male rats in NORT seems to be insensitive to CR treatments, since only young animals had ability 
to discriminate novel from old object.",
publisher = "Federation of European Biochemical Societies",
journal = "Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece",
title = "Calorie restriction changes long-term and short-term memory in rats in an  onset-, duration- and sex-dependent manner",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5324"
}

Prvulović, M., Todorović, S., Milanović, D., Vukojević, A., Simeunović, V., Jović, M., Sokanović, S.,& Mladenović, A.. (2022). Calorie restriction changes long-term and short-term memory in rats in an  onset-, duration- and sex-dependent manner. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece
Federation of European Biochemical Societies..
https://hdl.handle.net/21.15107/rcub_ibiss_5324

Prvulović M, Todorović S, Milanović D, Vukojević A, Simeunović V, Jović M, Sokanović S, Mladenović A. Calorie restriction changes long-term and short-term memory in rats in an  onset-, duration- and sex-dependent manner. in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5324 .

Prvulović, Milica, Todorović, Smilja, Milanović, Desanka, Vukojević, Anđela, Simeunović, Valentina, Jović, Milena, Sokanović, Srđan, Mladenović, Aleksandra, "Calorie restriction changes long-term and short-term memory in rats in an  onset-, duration- and sex-dependent manner" in Book of Abstracts: Joint IUBMB/FEBS Advanced Lecture Course: Molecular targets for anti-aging interventions; 2022 Sep 26 - Oct 1; Spetses Island, Greece (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5324 .

TY  - JOUR
AU  - Prvulović, Milica
AU  - Milanović, Desanka
AU  - Vujović, Predrag
AU  - Jović, Milena
AU  - Kanazir, Selma
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
PY  - 2021
UR  - https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glab353/6433769
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5436
AB  - The current study aims to determine the potential benefits of calorie restriction (CR), one of the most promising paradigms for life span and healthspan extension, on cognitive performances in female Wistar rats during aging. As a measure of a healthspan, we evaluated the effects of different onset and duration of CR on frailty level. Female Wistar rats were exposed to either ad libitum (AL) or CR (60% of AL daily intake) food intake during aging. Two different CR protocols were used, life-long CR with an early-onset that started at the adult stage (6 months) and 3-month-long CR, started at the middle (15 months) and late-middle (21 months) age, thus defined as a late-onset CR. The effects of CR were evaluated using open-field, Y-maze, and novel object recognition tests. We broadened 2 tools for frailty assessment currently in use for experimental animals, and in alignment with our previous study, we created a physical-cognitive frailty tool that combines both physical and cognitive performances. Our results clearly showed that CR effects are highly dependent on CR duration and onset. While a life-long restriction with an early-onset has been proven as protective and beneficial, short-term restriction introduced at late age significantly worsens an animal's behavior and frailty. These results complement our previous study conducted in males and contribute to the understanding of sex differences in a response to CR during aging.
T2  - The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences
T1  - Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats.
IS  - 5
VL  - 77
DO  - 10.1093/gerona/glab353
SP  - glab353
SP  - 947
EP  - 955
ER  - 

@article{
author = "Prvulović, Milica and Milanović, Desanka and Vujović, Predrag and Jović, Milena and Kanazir, Selma and Todorović, Smilja and Mladenović, Aleksandra",
year = "2021",
abstract = "The current study aims to determine the potential benefits of calorie restriction (CR), one of the most promising paradigms for life span and healthspan extension, on cognitive performances in female Wistar rats during aging. As a measure of a healthspan, we evaluated the effects of different onset and duration of CR on frailty level. Female Wistar rats were exposed to either ad libitum (AL) or CR (60% of AL daily intake) food intake during aging. Two different CR protocols were used, life-long CR with an early-onset that started at the adult stage (6 months) and 3-month-long CR, started at the middle (15 months) and late-middle (21 months) age, thus defined as a late-onset CR. The effects of CR were evaluated using open-field, Y-maze, and novel object recognition tests. We broadened 2 tools for frailty assessment currently in use for experimental animals, and in alignment with our previous study, we created a physical-cognitive frailty tool that combines both physical and cognitive performances. Our results clearly showed that CR effects are highly dependent on CR duration and onset. While a life-long restriction with an early-onset has been proven as protective and beneficial, short-term restriction introduced at late age significantly worsens an animal's behavior and frailty. These results complement our previous study conducted in males and contribute to the understanding of sex differences in a response to CR during aging.",
journal = "The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences",
title = "Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats.",
number = "5",
volume = "77",
doi = "10.1093/gerona/glab353",
pages = "glab353-947-955"
}

Prvulović, M., Milanović, D., Vujović, P., Jović, M., Kanazir, S., Todorović, S.,& Mladenović, A.. (2021). Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats.. in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 77(5), glab353-955.
https://doi.org/10.1093/gerona/glab353

Prvulović M, Milanović D, Vujović P, Jović M, Kanazir S, Todorović S, Mladenović A. Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats.. in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences. 2021;77(5):glab353-955.
doi:10.1093/gerona/glab353 .

Prvulović, Milica, Milanović, Desanka, Vujović, Predrag, Jović, Milena, Kanazir, Selma, Todorović, Smilja, Mladenović, Aleksandra, "Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats." in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 77, no. 5 (2021):glab353-955,
https://doi.org/10.1093/gerona/glab353 . .

TY  - CONF
AU  - Vukojević, Anđela
AU  - Prvulović, Milica
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
AU  - Jović, Milena
AU  - Jovanović-Macura, Irena
AU  - Perović, Milka
AU  - Milanović, Desanka
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5562
AB  - Non-communicable chronic diseases are largely driven by chronic inflammation, which can be in relation with poor diet and toxic products of commensal bacteria in guts. Diet intervention can change gut microbiota function and composition (Wastyk et al., 2021). The fermented foods containing microorganisms able to remodel host microbiota, can improve inflammatory status of the organism, including brain. Sauerkraut, produced by spontaneous fermentation of cabbage with lactic acid bacteria (LAB), is an important dietary ingredient, but studies of its effects are rather scarce (Zubaidah et al., 2020). Here, we aim to examine whether sauerkraut brine is able to change physiological and behavioral response to systemic inflammation in mice induced by lipopolysaccharides (LPS), a constituent of the Gram-negative bacteria cell wall (Kubera et al., 2016). 
Three-month-old C57BL/6 mice were given 150 l of sauerkraut brine (SB) or pasteurized sauerkraut brine (PSB) for 5 weeks by oral gavage. Control animals (CON) received the equivalent amount of water. During last week, animals were challenged by 5 injections of LPS (0.5 mg/kg, i.p.) Before and after LPS, behavior of animals was tested  by open field, light-dark box, Y-maze, tail-suspension and rota rod tests. Food consumption and body weight were measured throughout the experiment.
Quality analysis of in-home made sauerkraut produced by tradiotional spontaneous fermentation show that sauerkraut brine counts 2x105 colony forming units (CFU/ml) of LAB. SB and PSB treatments did not influence body weights and behavior compared to CON mice. LPS induced sick behavior characterized by weight loss and decreased food intake, where the fastest recovery was observed in the SB group. Behavioral analysis revealed similar response to LPS challenge between groups. However, further intra-group analysis and molecular screening is required to assess the possible subtle impact of sauerkraut on the mice behavior and immune status
PB  - Belgrade: Faculty of Chemistry: Serbian Biochemical Society
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - Effects of fermented food on the body weight and behavior after repeated LPS administration in mice
SP  - 179
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5562
ER  - 

@conference{
author = "Vukojević, Anđela and Prvulović, Milica and Todorović, Smilja and Mladenović, Aleksandra and Jović, Milena and Jovanović-Macura, Irena and Perović, Milka and Milanović, Desanka",
year = "2021",
abstract = "Non-communicable chronic diseases are largely driven by chronic inflammation, which can be in relation with poor diet and toxic products of commensal bacteria in guts. Diet intervention can change gut microbiota function and composition (Wastyk et al., 2021). The fermented foods containing microorganisms able to remodel host microbiota, can improve inflammatory status of the organism, including brain. Sauerkraut, produced by spontaneous fermentation of cabbage with lactic acid bacteria (LAB), is an important dietary ingredient, but studies of its effects are rather scarce (Zubaidah et al., 2020). Here, we aim to examine whether sauerkraut brine is able to change physiological and behavioral response to systemic inflammation in mice induced by lipopolysaccharides (LPS), a constituent of the Gram-negative bacteria cell wall (Kubera et al., 2016). 
Three-month-old C57BL/6 mice were given 150 l of sauerkraut brine (SB) or pasteurized sauerkraut brine (PSB) for 5 weeks by oral gavage. Control animals (CON) received the equivalent amount of water. During last week, animals were challenged by 5 injections of LPS (0.5 mg/kg, i.p.) Before and after LPS, behavior of animals was tested  by open field, light-dark box, Y-maze, tail-suspension and rota rod tests. Food consumption and body weight were measured throughout the experiment.
Quality analysis of in-home made sauerkraut produced by tradiotional spontaneous fermentation show that sauerkraut brine counts 2x105 colony forming units (CFU/ml) of LAB. SB and PSB treatments did not influence body weights and behavior compared to CON mice. LPS induced sick behavior characterized by weight loss and decreased food intake, where the fastest recovery was observed in the SB group. Behavioral analysis revealed similar response to LPS challenge between groups. However, further intra-group analysis and molecular screening is required to assess the possible subtle impact of sauerkraut on the mice behavior and immune status",
publisher = "Belgrade: Faculty of Chemistry: Serbian Biochemical Society",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "Effects of fermented food on the body weight and behavior after repeated LPS administration in mice",
pages = "179",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5562"
}

Vukojević, A., Prvulović, M., Todorović, S., Mladenović, A., Jović, M., Jovanović-Macura, I., Perović, M.,& Milanović, D.. (2021). Effects of fermented food on the body weight and behavior after repeated LPS administration in mice. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry: Serbian Biochemical Society., 179.
https://hdl.handle.net/21.15107/rcub_ibiss_5562

Vukojević A, Prvulović M, Todorović S, Mladenović A, Jović M, Jovanović-Macura I, Perović M, Milanović D. Effects of fermented food on the body weight and behavior after repeated LPS administration in mice. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:179.
https://hdl.handle.net/21.15107/rcub_ibiss_5562 .

Vukojević, Anđela, Prvulović, Milica, Todorović, Smilja, Mladenović, Aleksandra, Jović, Milena, Jovanović-Macura, Irena, Perović, Milka, Milanović, Desanka, "Effects of fermented food on the body weight and behavior after repeated LPS administration in mice" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):179,
https://hdl.handle.net/21.15107/rcub_ibiss_5562 .

TY  - JOUR
AU  - Prvulović, Milica
AU  - Milanović, Desanka
AU  - Vujović, Predrag
AU  - Jović, Milena
AU  - Kanazir, Selma
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
PY  - 2021
UR  - https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glab353/6433769
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4774
AB  - The current study aims to determine the potential benefits of calorie restriction (CR), one of the most promising paradigms for life span and healthspan extension, on cognitive performances in female Wistar rats during aging. As a measure of a healthspan, we evaluated the effects of different onset and duration of CR on frailty level. Female Wistar rats were exposed to either ad libitum (AL) or CR (60% of AL daily intake) food intake during aging. Two different CR protocols were used, life-long CR with an early-onset that started at the adult stage (6 months) and 3-month-long CR, started at the middle (15 months) and late-middle (21 months) age, thus defined as a late-onset CR. The effects of CR were evaluated using open-field, Y-maze, and novel object recognition tests. We broadened 2 tools for frailty assessment currently in use for experimental animals, and in alignment with our previous study, we created a physical-cognitive frailty tool that combines both physical and cognitive performances. Our results clearly showed that CR effects are highly dependent on CR duration and onset. While a life-long restriction with an early-onset has been proven as protective and beneficial, short-term restriction introduced at late age significantly worsens an animal's behavior and frailty. These results complement our previous study conducted in males and contribute to the understanding of sex differences in a response to CR during aging.
T2  - The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences
T1  - Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats.
IS  - 5
VL  - 77
DO  - 10.1093/gerona/glab353
SP  - glab353
SP  - 947
EP  - 955
ER  - 

@article{
author = "Prvulović, Milica and Milanović, Desanka and Vujović, Predrag and Jović, Milena and Kanazir, Selma and Todorović, Smilja and Mladenović, Aleksandra",
year = "2021",
abstract = "The current study aims to determine the potential benefits of calorie restriction (CR), one of the most promising paradigms for life span and healthspan extension, on cognitive performances in female Wistar rats during aging. As a measure of a healthspan, we evaluated the effects of different onset and duration of CR on frailty level. Female Wistar rats were exposed to either ad libitum (AL) or CR (60% of AL daily intake) food intake during aging. Two different CR protocols were used, life-long CR with an early-onset that started at the adult stage (6 months) and 3-month-long CR, started at the middle (15 months) and late-middle (21 months) age, thus defined as a late-onset CR. The effects of CR were evaluated using open-field, Y-maze, and novel object recognition tests. We broadened 2 tools for frailty assessment currently in use for experimental animals, and in alignment with our previous study, we created a physical-cognitive frailty tool that combines both physical and cognitive performances. Our results clearly showed that CR effects are highly dependent on CR duration and onset. While a life-long restriction with an early-onset has been proven as protective and beneficial, short-term restriction introduced at late age significantly worsens an animal's behavior and frailty. These results complement our previous study conducted in males and contribute to the understanding of sex differences in a response to CR during aging.",
journal = "The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences",
title = "Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats.",
number = "5",
volume = "77",
doi = "10.1093/gerona/glab353",
pages = "glab353-947-955"
}

Prvulović, M., Milanović, D., Vujović, P., Jović, M., Kanazir, S., Todorović, S.,& Mladenović, A.. (2021). Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats.. in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 77(5), glab353-955.
https://doi.org/10.1093/gerona/glab353

Prvulović M, Milanović D, Vujović P, Jović M, Kanazir S, Todorović S, Mladenović A. Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats.. in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences. 2021;77(5):glab353-955.
doi:10.1093/gerona/glab353 .

Prvulović, Milica, Milanović, Desanka, Vujović, Predrag, Jović, Milena, Kanazir, Selma, Todorović, Smilja, Mladenović, Aleksandra, "Late-Onset Calorie Restriction Worsens Cognitive Performances and Increases Frailty Level in Female Wistar Rats." in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 77, no. 5 (2021):glab353-955,
https://doi.org/10.1093/gerona/glab353 . .

TY  - JOUR
AU  - Mladenović, Aleksandra
AU  - Kapetanou, Marianna
AU  - Lončarević Vasiljković, Nataša
AU  - Todorović, Smilja
AU  - Athanasopoulou, Sofia
AU  - Jović, Milena
AU  - Prvulović, Milica
AU  - Taoufik, Era
AU  - Matsas, Rebecca
AU  - Kanazir, Selma
AU  - Gonos, Efstathios S.
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4074
AB  - Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by a progressive decline in a variety of cognitive and non-cognitive functions. The amyloid beta protein cascade hypothesis places the formation of amyloid beta protein aggregates on the first position in the complex pathological cascade leading to neurodegeneration, and therefore AD might be considered to be a protein-misfolding disease. The Ubiquitin Proteasome System (UPS), being the primary protein degradation mechanism with a fundamental role in the maintenance of proteostasis, has been identified as a putative therapeutic target to delay and/or to decelerate the progression of neurodegenerative disorders that are characterized by accumulated/aggregated proteins. The purpose of this study was to test if the activation of proteasome in vivo can alleviate AD pathology. Specifically by using two compounds with complementary modes of proteasome activation and documented antioxidant and redox regulating properties in the 5xFAD transgenic mice model of AD, we ameliorated a number of AD related deficits. Shortly after proteasome activation we detected significantly reduced amyloid-beta load correlated with improved motor functions, reduced anxiety and frailty level. Essentially, to our knowledge this is the first report to demonstrate a dual activation of the proteasome and its downstream effects. In conclusion, these findings open up new directions for future therapeutic potential of proteasome-mediated proteolysis enhancement.
PB  - Elsevier Inc.
T2  - Free Radical Biology and Medicine
T1  - Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation
VL  - 162
DO  - 10.1016/j.freeradbiomed.2020.11.038
SP  - 88
EP  - 103
ER  - 

@article{
author = "Mladenović, Aleksandra and Kapetanou, Marianna and Lončarević Vasiljković, Nataša and Todorović, Smilja and Athanasopoulou, Sofia and Jović, Milena and Prvulović, Milica and Taoufik, Era and Matsas, Rebecca and Kanazir, Selma and Gonos, Efstathios S.",
year = "2021",
abstract = "Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by a progressive decline in a variety of cognitive and non-cognitive functions. The amyloid beta protein cascade hypothesis places the formation of amyloid beta protein aggregates on the first position in the complex pathological cascade leading to neurodegeneration, and therefore AD might be considered to be a protein-misfolding disease. The Ubiquitin Proteasome System (UPS), being the primary protein degradation mechanism with a fundamental role in the maintenance of proteostasis, has been identified as a putative therapeutic target to delay and/or to decelerate the progression of neurodegenerative disorders that are characterized by accumulated/aggregated proteins. The purpose of this study was to test if the activation of proteasome in vivo can alleviate AD pathology. Specifically by using two compounds with complementary modes of proteasome activation and documented antioxidant and redox regulating properties in the 5xFAD transgenic mice model of AD, we ameliorated a number of AD related deficits. Shortly after proteasome activation we detected significantly reduced amyloid-beta load correlated with improved motor functions, reduced anxiety and frailty level. Essentially, to our knowledge this is the first report to demonstrate a dual activation of the proteasome and its downstream effects. In conclusion, these findings open up new directions for future therapeutic potential of proteasome-mediated proteolysis enhancement.",
publisher = "Elsevier Inc.",
journal = "Free Radical Biology and Medicine",
title = "Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation",
volume = "162",
doi = "10.1016/j.freeradbiomed.2020.11.038",
pages = "88-103"
}

Mladenović, A., Kapetanou, M., Lončarević Vasiljković, N., Todorović, S., Athanasopoulou, S., Jović, M., Prvulović, M., Taoufik, E., Matsas, R., Kanazir, S.,& Gonos, E. S.. (2021). Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation. in Free Radical Biology and Medicine
Elsevier Inc.., 162, 88-103.
https://doi.org/10.1016/j.freeradbiomed.2020.11.038

Mladenović A, Kapetanou M, Lončarević Vasiljković N, Todorović S, Athanasopoulou S, Jović M, Prvulović M, Taoufik E, Matsas R, Kanazir S, Gonos ES. Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation. in Free Radical Biology and Medicine. 2021;162:88-103.
doi:10.1016/j.freeradbiomed.2020.11.038 .

Mladenović, Aleksandra, Kapetanou, Marianna, Lončarević Vasiljković, Nataša, Todorović, Smilja, Athanasopoulou, Sofia, Jović, Milena, Prvulović, Milica, Taoufik, Era, Matsas, Rebecca, Kanazir, Selma, Gonos, Efstathios S., "Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation" in Free Radical Biology and Medicine, 162 (2021):88-103,
https://doi.org/10.1016/j.freeradbiomed.2020.11.038 . .