TY  - CONF
AU  - Sokanović, Srđan
AU  - Constantin, Stephanie
AU  - Lamarca Dams, Aloa
AU  - Mochimaru, Yuta
AU  - Smiljanić, Kosara
AU  - Bjelobaba, Ivana
AU  - Prévide, Rafael
AU  - Stojilković, Stanko
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5854
AB  - Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which 
encode the protein tyrosine phosphatase receptors N and N2, respectively, causes 
infertility of female mice while males are fertile. To clarify the mechanism of sex specific roles of Ptprn and Ptprn2 in mice reproduction, we analyzed the effects of 
their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO 
females, a delay in puberty and lack of ovulation were observed, supplemented by 
changes in ovarian gene expression and steroidogenesis. In DKO males, the testicular 
gene expression, steroidogenesis, and development of reproductive organs were not 
affected. However, in both sexes, pituitary luteinizing hormone (LH) beta gene
expression and LH levels were reduced, while the calcium-mobilizing and LH 
secretory actions of gonadotropin-releasing hormone (GnRH) receptors were 
preserved. The expression of hypothalamic Gnrh1 and Kiss1 genes were also reduced 
in DKO females and males. The density of immunoreactive GnRH fibers was 
decreased in the median eminence in DKO females and males. The density of 
immunoreactive kisspeptin fibers was also decreased in the rostral periventricular 
region of the third ventricle of females and in the arcuate nucleus of females and 
males. Therefore, infertility in DKO females cannot be explained only by sex-specific 
gonadotroph impairment. Instead, changes in hypothalamic gene expression, 
specifically Kiss1 in the rostral periventricular region of the third ventricle, might 
provide an alternative hypothesis due to its sexual dimorphism and involvement in 
puberty onset and ovulation.
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  - Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function
SP  - 107
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5854
ER  - 

@conference{
author = "Sokanović, Srđan and Constantin, Stephanie and Lamarca Dams, Aloa and Mochimaru, Yuta and Smiljanić, Kosara and Bjelobaba, Ivana and Prévide, Rafael and Stojilković, Stanko",
year = "2023",
abstract = "Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which 
encode the protein tyrosine phosphatase receptors N and N2, respectively, causes 
infertility of female mice while males are fertile. To clarify the mechanism of sex specific roles of Ptprn and Ptprn2 in mice reproduction, we analyzed the effects of 
their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO 
females, a delay in puberty and lack of ovulation were observed, supplemented by 
changes in ovarian gene expression and steroidogenesis. In DKO males, the testicular 
gene expression, steroidogenesis, and development of reproductive organs were not 
affected. However, in both sexes, pituitary luteinizing hormone (LH) beta gene
expression and LH levels were reduced, while the calcium-mobilizing and LH 
secretory actions of gonadotropin-releasing hormone (GnRH) receptors were 
preserved. The expression of hypothalamic Gnrh1 and Kiss1 genes were also reduced 
in DKO females and males. The density of immunoreactive GnRH fibers was 
decreased in the median eminence in DKO females and males. The density of 
immunoreactive kisspeptin fibers was also decreased in the rostral periventricular 
region of the third ventricle of females and in the arcuate nucleus of females and 
males. Therefore, infertility in DKO females cannot be explained only by sex-specific 
gonadotroph impairment. Instead, changes in hypothalamic gene expression, 
specifically Kiss1 in the rostral periventricular region of the third ventricle, might 
provide an alternative hypothesis due to its sexual dimorphism and involvement in 
puberty onset and ovulation.",
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 = "Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function",
pages = "107",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5854"
}

Sokanović, S., Constantin, S., Lamarca Dams, A., Mochimaru, Y., Smiljanić, K., Bjelobaba, I., Prévide, R.,& Stojilković, S.. (2023). Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 107.
https://hdl.handle.net/21.15107/rcub_ibiss_5854

Sokanović S, Constantin S, Lamarca Dams A, Mochimaru Y, Smiljanić K, Bjelobaba I, Prévide R, Stojilković S. Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:107.
https://hdl.handle.net/21.15107/rcub_ibiss_5854 .

Sokanović, Srđan, Constantin, Stephanie, Lamarca Dams, Aloa, Mochimaru, Yuta, Smiljanić, Kosara, Bjelobaba, Ivana, Prévide, Rafael, Stojilković, Stanko, "Protein tyrosine phosphatase receptors N and N2 regulate  gonadotropin-releasing hormone neuron function" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):107,
https://hdl.handle.net/21.15107/rcub_ibiss_5854 .

TY  - JOUR
AU  - Sokanović, Srđan
AU  - Constantin, Stephanie
AU  - Dams, Aloa Lamarca
AU  - Mochimaru, Yuta
AU  - Smiljanić, Kosara
AU  - Bjelobaba, Ivana
AU  - Prévide, Rafael
AU  - Stojilković, Stanko
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5382
AB  - Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which encode the protein tyrosine phosphatase receptors N and N2, causes infertility in female mice while males are fertile. To elucidate the mechanism of the sex-specific roles of Ptprn and Ptprn2 in mouse reproduction, we analyzed the effects of their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO females, delayed puberty and lack of ovulation were observed, complemented by changes in ovarian gene expression and steroidogenesis. In contrast, testicular gene expression, steroidogenesis, and reproductive organs development were not significantly affected in DKO males. However, in both sexes, pituitary luteinizing hormone (LH) beta gene expression and LH levels were reduced, as well as follicle-stimulating hormone beta gene and gonadotropin-releasing hormone (GnRH) gene, while the calcium-mobilizing and LH secretory actions of GnRH were preserved. Hypothalamic Gnrh1 and Kiss1 gene expression was also reduced in DKO females and males. In parallel, a significant decrease in the density of immunoreactive GnRH and kisspeptin fibers was detected in the hypothalamic arcuate nucleus of DKO females and males. The female-specific kisspeptin immunoreactivity in the rostral periventricular region of the third ventricle was also reduced in DKO females, but not in DKO males. These data indicate a critical role of Ptprn and Ptprn2 in kisspeptin-GnRH neuronal function and sexual dimorphism in the threshold levels of GnRH required to preserve reproductive functions.
PB  - Springer Nature
T2  - Scientific Reports
T1  - Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction
VL  - 13
DO  - 10.1038/s41598-023-27497-4
SP  - 1
SP  - 355
ER  - 

@article{
author = "Sokanović, Srđan and Constantin, Stephanie and Dams, Aloa Lamarca and Mochimaru, Yuta and Smiljanić, Kosara and Bjelobaba, Ivana and Prévide, Rafael and Stojilković, Stanko",
year = "2023",
abstract = "Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which encode the protein tyrosine phosphatase receptors N and N2, causes infertility in female mice while males are fertile. To elucidate the mechanism of the sex-specific roles of Ptprn and Ptprn2 in mouse reproduction, we analyzed the effects of their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In DKO females, delayed puberty and lack of ovulation were observed, complemented by changes in ovarian gene expression and steroidogenesis. In contrast, testicular gene expression, steroidogenesis, and reproductive organs development were not significantly affected in DKO males. However, in both sexes, pituitary luteinizing hormone (LH) beta gene expression and LH levels were reduced, as well as follicle-stimulating hormone beta gene and gonadotropin-releasing hormone (GnRH) gene, while the calcium-mobilizing and LH secretory actions of GnRH were preserved. Hypothalamic Gnrh1 and Kiss1 gene expression was also reduced in DKO females and males. In parallel, a significant decrease in the density of immunoreactive GnRH and kisspeptin fibers was detected in the hypothalamic arcuate nucleus of DKO females and males. The female-specific kisspeptin immunoreactivity in the rostral periventricular region of the third ventricle was also reduced in DKO females, but not in DKO males. These data indicate a critical role of Ptprn and Ptprn2 in kisspeptin-GnRH neuronal function and sexual dimorphism in the threshold levels of GnRH required to preserve reproductive functions.",
publisher = "Springer Nature",
journal = "Scientific Reports",
title = "Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction",
volume = "13",
doi = "10.1038/s41598-023-27497-4",
pages = "1-355"
}

Sokanović, S., Constantin, S., Dams, A. L., Mochimaru, Y., Smiljanić, K., Bjelobaba, I., Prévide, R.,& Stojilković, S.. (2023). Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction. in Scientific Reports
Springer Nature., 13, 1.
https://doi.org/10.1038/s41598-023-27497-4

Sokanović S, Constantin S, Dams AL, Mochimaru Y, Smiljanić K, Bjelobaba I, Prévide R, Stojilković S. Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction. in Scientific Reports. 2023;13:1.
doi:10.1038/s41598-023-27497-4 .

Sokanović, Srđan, Constantin, Stephanie, Dams, Aloa Lamarca, Mochimaru, Yuta, Smiljanić, Kosara, Bjelobaba, Ivana, Prévide, Rafael, Stojilković, Stanko, "Common and female-specific roles of proteine tyrosine phosphatase receptors N and N2 in mice reproduction" in Scientific Reports, 13 (2023):1,
https://doi.org/10.1038/s41598-023-27497-4 . .

TY  - JOUR
AU  - Dominko, Kristina
AU  - Rastija, Ana
AU  - Smiljanić, Kosara
AU  - Mladenović, Aleksandra
AU  - Lešnjaković, Lucija
AU  - Kanazir, Selma
AU  - Milanović, Desanka
AU  - Hećimović, Silva
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0047637422001087
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5109
AB  - The formation of amyloid-ß peptides (Aß), that accumulate in Alzheimer's disease (AD) brains, involves proteolytic processing of the amyloid precursor protein (APP) firstly by ß-secretase (BACE1). Since BACE1 cleaves a plethora of other substrates, in this work we investigated whether the proteolysis and/or distribution of other BACE1 substrates, such as seizure protein 6 (Sez6) and seizure 6-like protein (Sez6L), is altered in AD. To test this we used 5xFAD mouse model brains that show an early accumulation of Aß plaques already at 2-months of age. Here we show for the first time that accumulation of BACE1 in peri-plaque regions and its enhanced levels in AD brains does not affect proteolysis of BACE1 substrates other than APP, such as Sez6 and Sez6L. We observed altered distribution of Sez6 and Sez6L in the area of Aß plaques in 5xFAD brains which is distinct to that of APP, BACE1 and/or LAMP1, suggesting different localization and/or function of these BACE1 substrates. While it is necessary to further elucidate the potential role that this may play in the course of AD, it is likely that Aß-targeted therapies may have beneficial effects against accumulation and/or altered distribution of BACE1 and its substrates, in addition to APP.
PB  - Clare: Elsevier Ireland Ltd.
T2  - Mechanisms of Ageing and Development
T1  - Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L.
VL  - 207
DO  - 10.1016/j.mad.2022.111726
SP  - 111726
ER  - 

@article{
author = "Dominko, Kristina and Rastija, Ana and Smiljanić, Kosara and Mladenović, Aleksandra and Lešnjaković, Lucija and Kanazir, Selma and Milanović, Desanka and Hećimović, Silva",
year = "2022",
abstract = "The formation of amyloid-ß peptides (Aß), that accumulate in Alzheimer's disease (AD) brains, involves proteolytic processing of the amyloid precursor protein (APP) firstly by ß-secretase (BACE1). Since BACE1 cleaves a plethora of other substrates, in this work we investigated whether the proteolysis and/or distribution of other BACE1 substrates, such as seizure protein 6 (Sez6) and seizure 6-like protein (Sez6L), is altered in AD. To test this we used 5xFAD mouse model brains that show an early accumulation of Aß plaques already at 2-months of age. Here we show for the first time that accumulation of BACE1 in peri-plaque regions and its enhanced levels in AD brains does not affect proteolysis of BACE1 substrates other than APP, such as Sez6 and Sez6L. We observed altered distribution of Sez6 and Sez6L in the area of Aß plaques in 5xFAD brains which is distinct to that of APP, BACE1 and/or LAMP1, suggesting different localization and/or function of these BACE1 substrates. While it is necessary to further elucidate the potential role that this may play in the course of AD, it is likely that Aß-targeted therapies may have beneficial effects against accumulation and/or altered distribution of BACE1 and its substrates, in addition to APP.",
publisher = "Clare: Elsevier Ireland Ltd.",
journal = "Mechanisms of Ageing and Development",
title = "Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L.",
volume = "207",
doi = "10.1016/j.mad.2022.111726",
pages = "111726"
}

Dominko, K., Rastija, A., Smiljanić, K., Mladenović, A., Lešnjaković, L., Kanazir, S., Milanović, D.,& Hećimović, S.. (2022). Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L.. in Mechanisms of Ageing and Development
Clare: Elsevier Ireland Ltd.., 207, 111726.
https://doi.org/10.1016/j.mad.2022.111726

Dominko K, Rastija A, Smiljanić K, Mladenović A, Lešnjaković L, Kanazir S, Milanović D, Hećimović S. Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L.. in Mechanisms of Ageing and Development. 2022;207:111726.
doi:10.1016/j.mad.2022.111726 .

Dominko, Kristina, Rastija, Ana, Smiljanić, Kosara, Mladenović, Aleksandra, Lešnjaković, Lucija, Kanazir, Selma, Milanović, Desanka, Hećimović, Silva, "Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L." in Mechanisms of Ageing and Development, 207 (2022):111726,
https://doi.org/10.1016/j.mad.2022.111726 . .

TY  - CHAP
AU  - Smiljanić, Kosara
AU  - Lončarević-Vasiljković, Nataša
AU  - Kanazir, Selma
AU  - Mladenović, Aleksandra
PY  - 2020
UR  - http://www.eurekaselect.com/node/182407
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3965
AB  - Cholesterol is the molecule essential for life, but also with a possible detrimental role. Apart from being a vital structural constituent of the cells, cholesterol is a factor involved in many important cell processes. However, it has been known that high blood cholesterol is associated with many pathological conditions. An elevated level of cholesterol is linked with cardiovascular disease, diabetes and neurodegenerative disorders. Almost quarter of the total cholesterol in the body resides in the brain. This vast pool is synthesized in situ and it is almost completely isolated and independent from the periphery due to the presence of blood-brain barrier. In the central nervous system, cholesterol plays important role in neural cells structure and functions, including synaptic transmission. Due to this, its content must be precisely maintained in order to keep brain function well. However, cholesterol is critically challenged in the aging brain and disturbed in several of pathological conditions, like Huntington’s disease (HD), Parkinson’s disease (PD), Niemann-Pick type C (NPC) disease and Smith-Lemli Opitz syndrome (SLOS), traumatic brain injury, multiple sclerosis (MS) and in Alzheimer’s disease (AD). Altered cholesterol metabolism has been extensively implicated in the pathogenesis of AD. A growing amount of evidence underscores the link between disturbed intracellular trafficking of cholesterol in the brain and the formation of amyloid plaques. The inheritance of the epsilon4 allele of the Apolipoprotein E (ApoE), the main transport protein for cholesterol in the brain represents the main risk factor for late onset form of Alzheimer’s disease. Other genetic polymorphisms associated with critical points in cholesterol metabolism may also contribute to the AD pathogenesis. Hypercholesterolemia has been considered nowadays also as a risk factor, and all of these players are thought to promote the production of beta-amyloid and development of AD. Additional proof towards cholesterol involvement in the pathogenesis of AD gave epidemiological data of the cholesterol-lowering drugs, statins that have been shown to decrease the risk for AD. This chapter is aimed to summarize existing knowledge about the brain cholesterol metabolism, how the homeostasis is changed during aging and in various neurodegenerative diseases, with special emphasis on Alzheimer’s disease. As a final point, we will try to give a full insight into the environmental influences (including dietary restriction and statins therapy) on brain cholesterol homeostasis.
PB  - Bentham Science Publishers
T2  - Frontiers in Clinical Drug Research-Dementia
T1  - Cholesterol in Brain Health and Pathologies: The Role in Alzheimer’s Disease
DO  - 10.2174/9789811410949120010004
SP  - 26
EP  - 77
ER  - 

@inbook{
editor = "Atta-ur-Rahman",
author = "Smiljanić, Kosara and Lončarević-Vasiljković, Nataša and Kanazir, Selma and Mladenović, Aleksandra",
year = "2020",
abstract = "Cholesterol is the molecule essential for life, but also with a possible detrimental role. Apart from being a vital structural constituent of the cells, cholesterol is a factor involved in many important cell processes. However, it has been known that high blood cholesterol is associated with many pathological conditions. An elevated level of cholesterol is linked with cardiovascular disease, diabetes and neurodegenerative disorders. Almost quarter of the total cholesterol in the body resides in the brain. This vast pool is synthesized in situ and it is almost completely isolated and independent from the periphery due to the presence of blood-brain barrier. In the central nervous system, cholesterol plays important role in neural cells structure and functions, including synaptic transmission. Due to this, its content must be precisely maintained in order to keep brain function well. However, cholesterol is critically challenged in the aging brain and disturbed in several of pathological conditions, like Huntington’s disease (HD), Parkinson’s disease (PD), Niemann-Pick type C (NPC) disease and Smith-Lemli Opitz syndrome (SLOS), traumatic brain injury, multiple sclerosis (MS) and in Alzheimer’s disease (AD). Altered cholesterol metabolism has been extensively implicated in the pathogenesis of AD. A growing amount of evidence underscores the link between disturbed intracellular trafficking of cholesterol in the brain and the formation of amyloid plaques. The inheritance of the epsilon4 allele of the Apolipoprotein E (ApoE), the main transport protein for cholesterol in the brain represents the main risk factor for late onset form of Alzheimer’s disease. Other genetic polymorphisms associated with critical points in cholesterol metabolism may also contribute to the AD pathogenesis. Hypercholesterolemia has been considered nowadays also as a risk factor, and all of these players are thought to promote the production of beta-amyloid and development of AD. Additional proof towards cholesterol involvement in the pathogenesis of AD gave epidemiological data of the cholesterol-lowering drugs, statins that have been shown to decrease the risk for AD. This chapter is aimed to summarize existing knowledge about the brain cholesterol metabolism, how the homeostasis is changed during aging and in various neurodegenerative diseases, with special emphasis on Alzheimer’s disease. As a final point, we will try to give a full insight into the environmental influences (including dietary restriction and statins therapy) on brain cholesterol homeostasis.",
publisher = "Bentham Science Publishers",
journal = "Frontiers in Clinical Drug Research-Dementia",
booktitle = "Cholesterol in Brain Health and Pathologies: The Role in Alzheimer’s Disease",
doi = "10.2174/9789811410949120010004",
pages = "26-77"
}

Atta-ur-Rahman, Smiljanić, K., Lončarević-Vasiljković, N., Kanazir, S.,& Mladenović, A.. (2020). Cholesterol in Brain Health and Pathologies: The Role in Alzheimer’s Disease. in Frontiers in Clinical Drug Research-Dementia
Bentham Science Publishers., 26-77.
https://doi.org/10.2174/9789811410949120010004

Atta-ur-Rahman, Smiljanić K, Lončarević-Vasiljković N, Kanazir S, Mladenović A. Cholesterol in Brain Health and Pathologies: The Role in Alzheimer’s Disease. in Frontiers in Clinical Drug Research-Dementia. 2020;:26-77.
doi:10.2174/9789811410949120010004 .

Atta-ur-Rahman, Smiljanić, Kosara, Lončarević-Vasiljković, Nataša, Kanazir, Selma, Mladenović, Aleksandra, "Cholesterol in Brain Health and Pathologies: The Role in Alzheimer’s Disease" in Frontiers in Clinical Drug Research-Dementia (2020):26-77,
https://doi.org/10.2174/9789811410949120010004 . .

TY  - CONF
AU  - Janjić, Marija
AU  - Previde, Rafael Maso
AU  - Smiljanić, Kosara
AU  - Fletcher, Patrick A.
AU  - Sherman, Arthur
AU  - Bjelobaba, Ivana
AU  - Stojilkovic, Stanko S.
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5981
AB  - Aim: To investigate mechanisms of inhibition of reproductive functions by continuous GnRH application, with focus on gonadotropin gene expression and secretion. Methods: Experiments were performed in vivo and in vitro using female and male rats and cultured pituitary cells. Gene expression was characterized by qRT-PCR analysis. For this purpose, we searched for an appropriate reference gene. Protein expression was characterized by immunocytochemistry, and ELISA and Western blot analyses were used for LH measurements. Results: Continuous exposure of pituitary cells in static cultures to Gnrh agonists induced a prolonged blockade of Fshb expression after a brief stimulation. However, only a minor and transient inhibitory effect on Lhb expression was detected. Such Lhb profile probably reflects the expression status of three genes controlling Lhb transcription during the treatment: stimulation of Egr1, inhibition of Nr5a1, and no effect on Pitx1 expression. In contrast, continuous Gnrh treatment stimulated Lh secretion in static cultures, leading to depletion of the secretory pool. In vivo administration of a Gnrh agonist was also accompanied with a rapid increase in serum Lh levels and a progressive depletion of the intrapituitary Lh levels without major effects on Lhb expression. Conclusion: Blockade of Fshb expression and depletion of the Lh secretory pool are two major factors accounting for weakening of the gonadotroph secretory function during continuous Gnrh treatment.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs
SP  - 367
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5981
ER  - 

@conference{
author = "Janjić, Marija and Previde, Rafael Maso and Smiljanić, Kosara and Fletcher, Patrick A. and Sherman, Arthur and Bjelobaba, Ivana and Stojilkovic, Stanko S.",
year = "2019",
abstract = "Aim: To investigate mechanisms of inhibition of reproductive functions by continuous GnRH application, with focus on gonadotropin gene expression and secretion. Methods: Experiments were performed in vivo and in vitro using female and male rats and cultured pituitary cells. Gene expression was characterized by qRT-PCR analysis. For this purpose, we searched for an appropriate reference gene. Protein expression was characterized by immunocytochemistry, and ELISA and Western blot analyses were used for LH measurements. Results: Continuous exposure of pituitary cells in static cultures to Gnrh agonists induced a prolonged blockade of Fshb expression after a brief stimulation. However, only a minor and transient inhibitory effect on Lhb expression was detected. Such Lhb profile probably reflects the expression status of three genes controlling Lhb transcription during the treatment: stimulation of Egr1, inhibition of Nr5a1, and no effect on Pitx1 expression. In contrast, continuous Gnrh treatment stimulated Lh secretion in static cultures, leading to depletion of the secretory pool. In vivo administration of a Gnrh agonist was also accompanied with a rapid increase in serum Lh levels and a progressive depletion of the intrapituitary Lh levels without major effects on Lhb expression. Conclusion: Blockade of Fshb expression and depletion of the Lh secretory pool are two major factors accounting for weakening of the gonadotroph secretory function during continuous Gnrh treatment.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs",
pages = "367",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5981"
}

Janjić, M., Previde, R. M., Smiljanić, K., Fletcher, P. A., Sherman, A., Bjelobaba, I.,& Stojilkovic, S. S.. (2019). Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 367.
https://hdl.handle.net/21.15107/rcub_ibiss_5981

Janjić M, Previde RM, Smiljanić K, Fletcher PA, Sherman A, Bjelobaba I, Stojilkovic SS. Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:367.
https://hdl.handle.net/21.15107/rcub_ibiss_5981 .

Janjić, Marija, Previde, Rafael Maso, Smiljanić, Kosara, Fletcher, Patrick A., Sherman, Arthur, Bjelobaba, Ivana, Stojilkovic, Stanko S., "Continuous GnRH Treatment Blocks Basal Fshb but not Lhb Expression in Rat Pituitary Gonadotrophs" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):367,
https://hdl.handle.net/21.15107/rcub_ibiss_5981 .

TY  - CONF
AU  - Prvulović, Milica
AU  - Smiljanić, Kosara
AU  - Todorović, Smilja
AU  - Kanazir, Selma
AU  - Mladenović, Aleksandra
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5855
AB  - Aims: Food restriction (FR) ¬is well known as an environmental intervention efficient in delaying aging and age-related disorders. Important role in the regulation of food intake plays the gut-brain dopamine (DA) axis. Dopamine is a neurotransmitter involved in regulation of brain’s rewarding and pleasure centers, who’s signaling is indispensable to survival and maintenance of eating patterns. Reversely, reduced food intake affects DA circuits and behaviors controlled by DA, including anxiety. Herein we investigated mechanisms through which FR affects anxiety and the role of dopaminergic system in this process. 
Methods: 60% FR of various onset and duration (FR1, FR2 and FR3) was implemented as a feeding regime for aging male Wistar rats. Open field test and light-dark box were used to investigate effects of age and food restriction on anxiety-like behavior. Western blot and PCR were used to determine the changes at the transcriptional and translational level.
Results: Open field test showed an increased general activity of animals under FR1 in comparison to the controls, while FR2 and FR3 seemed to have deleterious effect on anxiety level. Light-dark box confirmed deleterious effect of FR2 and FR3 regimens.  Changes detected on behavioral level were accompanied with the specific changes in the level of dopaminergic receptors.
Conclusions: Our results showed that food restriction is not universally beneficial, but depends on age when implemented. We showed that FR-induced effects can vary from anxiolytic to anxiogenic, while the components of DA circuits in the brain show region-specific response to FR.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - The effects of food restriction on anxiety level and dopaminergic system during aging in male Wistar rats
SP  - 73
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5855
ER  - 

@conference{
author = "Prvulović, Milica and Smiljanić, Kosara and Todorović, Smilja and Kanazir, Selma and Mladenović, Aleksandra",
year = "2019",
abstract = "Aims: Food restriction (FR) ¬is well known as an environmental intervention efficient in delaying aging and age-related disorders. Important role in the regulation of food intake plays the gut-brain dopamine (DA) axis. Dopamine is a neurotransmitter involved in regulation of brain’s rewarding and pleasure centers, who’s signaling is indispensable to survival and maintenance of eating patterns. Reversely, reduced food intake affects DA circuits and behaviors controlled by DA, including anxiety. Herein we investigated mechanisms through which FR affects anxiety and the role of dopaminergic system in this process. 
Methods: 60% FR of various onset and duration (FR1, FR2 and FR3) was implemented as a feeding regime for aging male Wistar rats. Open field test and light-dark box were used to investigate effects of age and food restriction on anxiety-like behavior. Western blot and PCR were used to determine the changes at the transcriptional and translational level.
Results: Open field test showed an increased general activity of animals under FR1 in comparison to the controls, while FR2 and FR3 seemed to have deleterious effect on anxiety level. Light-dark box confirmed deleterious effect of FR2 and FR3 regimens.  Changes detected on behavioral level were accompanied with the specific changes in the level of dopaminergic receptors.
Conclusions: Our results showed that food restriction is not universally beneficial, but depends on age when implemented. We showed that FR-induced effects can vary from anxiolytic to anxiogenic, while the components of DA circuits in the brain show region-specific response to FR.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "The effects of food restriction on anxiety level and dopaminergic system during aging in male Wistar rats",
pages = "73",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5855"
}

Prvulović, M., Smiljanić, K., Todorović, S., Kanazir, S.,& Mladenović, A.. (2019). The effects of food restriction on anxiety level and dopaminergic system during aging in male Wistar rats. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 73.
https://hdl.handle.net/21.15107/rcub_ibiss_5855

Prvulović M, Smiljanić K, Todorović S, Kanazir S, Mladenović A. The effects of food restriction on anxiety level and dopaminergic system during aging in male Wistar rats. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2019;:73.
https://hdl.handle.net/21.15107/rcub_ibiss_5855 .

Prvulović, Milica, Smiljanić, Kosara, Todorović, Smilja, Kanazir, Selma, Mladenović, Aleksandra, "The effects of food restriction on anxiety level and dopaminergic system during aging in male Wistar rats" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2019):73,
https://hdl.handle.net/21.15107/rcub_ibiss_5855 .

TY  - CONF
AU  - Prvulović, Milica
AU  - Smiljanić, Kosara
AU  - Todorović, Smilja
AU  - Kanazir, Selma
AU  - Mladenović, Aleksandra
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5717
AB  - Aims: Dietary restriction (DR) has numerous beneficial effects on organism, starting from positive effect on life expectancy, to protective effects on cardiovascular system, blood lipid levels, immune response, glucoregulation, and neurological functions. Previously it has been shown that DR changes expression of genes and proteins involved in cholesterol metabolism, in both cerebral cortex and hippocampus. Herein we investigated cholesterol homeostasis in  cerebellum, as a brain structure involved in motor and cognitive functions. 
Methods: We examined the effect of 4 different DR regimens (intermittent fasting and limited daily feeding of various onset and duration), on cholesterol metabolism in cerebellum of aging male Wistar rats. We used western blot to examine changes in the level of proteins playing the major roles in cholesterol biosynthesis (SREBP1 and HMGCR), transport (ApoE and LRP1) and elimination from the brain (CYP46).
Results: Detected changes in the expression level of selected proteins indicated that the effect of DR is highly dependent on the type of dietary regimen and the age when implemented. Positive effect is mainly noticed in the group of 18 months old rats.
Conclusions: This study showed the potential of dietary restriction as an alternative to pharmacological treatment of high blood cholesterol levels  and confirmed beneficial effects of DR as a  healthy lifestyle in prevention of age related disorders.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats
SP  - 497
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5717
ER  - 

@conference{
author = "Prvulović, Milica and Smiljanić, Kosara and Todorović, Smilja and Kanazir, Selma and Mladenović, Aleksandra",
year = "2019",
abstract = "Aims: Dietary restriction (DR) has numerous beneficial effects on organism, starting from positive effect on life expectancy, to protective effects on cardiovascular system, blood lipid levels, immune response, glucoregulation, and neurological functions. Previously it has been shown that DR changes expression of genes and proteins involved in cholesterol metabolism, in both cerebral cortex and hippocampus. Herein we investigated cholesterol homeostasis in  cerebellum, as a brain structure involved in motor and cognitive functions. 
Methods: We examined the effect of 4 different DR regimens (intermittent fasting and limited daily feeding of various onset and duration), on cholesterol metabolism in cerebellum of aging male Wistar rats. We used western blot to examine changes in the level of proteins playing the major roles in cholesterol biosynthesis (SREBP1 and HMGCR), transport (ApoE and LRP1) and elimination from the brain (CYP46).
Results: Detected changes in the expression level of selected proteins indicated that the effect of DR is highly dependent on the type of dietary regimen and the age when implemented. Positive effect is mainly noticed in the group of 18 months old rats.
Conclusions: This study showed the potential of dietary restriction as an alternative to pharmacological treatment of high blood cholesterol levels  and confirmed beneficial effects of DR as a  healthy lifestyle in prevention of age related disorders.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats",
pages = "497",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5717"
}

Prvulović, M., Smiljanić, K., Todorović, S., Kanazir, S.,& Mladenović, A.. (2019). The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 497.
https://hdl.handle.net/21.15107/rcub_ibiss_5717

Prvulović M, Smiljanić K, Todorović S, Kanazir S, Mladenović A. The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:497.
https://hdl.handle.net/21.15107/rcub_ibiss_5717 .

Prvulović, Milica, Smiljanić, Kosara, Todorović, Smilja, Kanazir, Selma, Mladenović, Aleksandra, "The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):497,
https://hdl.handle.net/21.15107/rcub_ibiss_5717 .

TY  - JOUR
AU  - Janjić, Marija
AU  - Prévide, Rafael M.
AU  - Fletcher, Patrick A.
AU  - Sherman, Arthur
AU  - Smiljanić, Kosara
AU  - Abebe, Daniel
AU  - Bjelobaba, Ivana
AU  - Stojilković, Stanko S.
PY  - 2019
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6934515
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3595
AB  - Continuous, as opposed to pulsatile, delivery of hypothalamic gonadotropin-releasing hormone (GnRH) leads to a marked decrease in secretion of pituitary gonadotropins LH and FSH and impairment of reproductive function. Here we studied the expression profile of gonadotropin subunit and GnRH receptor genes in rat pituitary in vitro and in vivo to clarify their expression profiles in the absence and continuous presence of GnRH. Culturing of pituitary cells in GnRH-free conditions downregulated Fshb, Cga, and Gnrhr expression, whereas continuous treatment with GnRH agonists upregulated Cga expression progressively and Gnrhr and Fshb expression transiently, accompanied by a prolonged blockade of Fshb but not Gnrhr expression. In contrast, Lhb expression was relatively insensitive to loss of endogenous GnRH and continuous treatment with GnRH, probably reflecting the status of Egr1 and Nr5a1 expression. Similar patterns of responses were observed in vivo after administration of a GnRH agonist. However, continuous treatment with GnRH stimulated LH secretion in vitro and in vivo, leading to decrease in LH cell content despite high basal Lhb expression. These data suggest that blockade of Fshb expression and depletion of the LH secretory pool are two major factors accounting for weakening of the gonadotroph secretory function during continuous GnRH treatment.
T2  - Scientific Reports
T1  - Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo.
IS  - 1
VL  - 9
DO  - 10.1038/s41598-019-56480-1
SP  - 20098
ER  - 

@article{
author = "Janjić, Marija and Prévide, Rafael M. and Fletcher, Patrick A. and Sherman, Arthur and Smiljanić, Kosara and Abebe, Daniel and Bjelobaba, Ivana and Stojilković, Stanko S.",
year = "2019",
abstract = "Continuous, as opposed to pulsatile, delivery of hypothalamic gonadotropin-releasing hormone (GnRH) leads to a marked decrease in secretion of pituitary gonadotropins LH and FSH and impairment of reproductive function. Here we studied the expression profile of gonadotropin subunit and GnRH receptor genes in rat pituitary in vitro and in vivo to clarify their expression profiles in the absence and continuous presence of GnRH. Culturing of pituitary cells in GnRH-free conditions downregulated Fshb, Cga, and Gnrhr expression, whereas continuous treatment with GnRH agonists upregulated Cga expression progressively and Gnrhr and Fshb expression transiently, accompanied by a prolonged blockade of Fshb but not Gnrhr expression. In contrast, Lhb expression was relatively insensitive to loss of endogenous GnRH and continuous treatment with GnRH, probably reflecting the status of Egr1 and Nr5a1 expression. Similar patterns of responses were observed in vivo after administration of a GnRH agonist. However, continuous treatment with GnRH stimulated LH secretion in vitro and in vivo, leading to decrease in LH cell content despite high basal Lhb expression. These data suggest that blockade of Fshb expression and depletion of the LH secretory pool are two major factors accounting for weakening of the gonadotroph secretory function during continuous GnRH treatment.",
journal = "Scientific Reports",
title = "Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo.",
number = "1",
volume = "9",
doi = "10.1038/s41598-019-56480-1",
pages = "20098"
}

Janjić, M., Prévide, R. M., Fletcher, P. A., Sherman, A., Smiljanić, K., Abebe, D., Bjelobaba, I.,& Stojilković, S. S.. (2019). Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo.. in Scientific Reports, 9(1), 20098.
https://doi.org/10.1038/s41598-019-56480-1

Janjić M, Prévide RM, Fletcher PA, Sherman A, Smiljanić K, Abebe D, Bjelobaba I, Stojilković SS. Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo.. in Scientific Reports. 2019;9(1):20098.
doi:10.1038/s41598-019-56480-1 .

Janjić, Marija, Prévide, Rafael M., Fletcher, Patrick A., Sherman, Arthur, Smiljanić, Kosara, Abebe, Daniel, Bjelobaba, Ivana, Stojilković, Stanko S., "Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo." in Scientific Reports, 9, no. 1 (2019):20098,
https://doi.org/10.1038/s41598-019-56480-1 . .

TY  - JOUR
AU  - Todorović, Smilja
AU  - Smiljanić, Kosara
AU  - Ruždijić, Sabera
AU  - Mladenović, Aleksandra
AU  - Kanazir, Selma
PY  - 2018
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037071/
UR  - https://academic.oup.com/biomedgerontology/article/73/8/1036/4837193
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3541
AB  - Dietary restriction (DR) is an important experimental paradigm for lifespan and healthspan extension, but its specific contribution regarding the type, onset, and duration are still debatable. This study was designed to examine the impact of different dietary protocols by assessing the behavioral changes during aging. We exposed male Wistar rats of various age to ad libitum (AL) or DR (60 per cent of AL daily intake) feeding regimens with different onsets. The impact of DR on locomotor activity, memory, and learning was examined in 12-, 18-, and 24-month-old treated animals and controls using open field and Y-maze tests. We have also evaluated the effects of different DR's through the quantification of animal frailty, using behavioral data to create the frailty score. Our results indicated that DR improves general animal activity and spatial memory and decreases frailty with the effect being highly dependent on DR duration and onset. Notably, life-long restriction started at young age had the most profound effect. In contrast, shorter duration and later onset of restricted diet had significantly lower or no impact on animal's behavior and frailty. This study signifies the importance of DR starting point and duration as critical determinants of DR effects on healthspan.
T2  - The Journals of Gerontology: Series A
T1  - Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging
IS  - 8
VL  - 73
DO  - 10.1093/gerona/gly015
SP  - 1036
EP  - 1044
ER  - 

@article{
author = "Todorović, Smilja and Smiljanić, Kosara and Ruždijić, Sabera and Mladenović, Aleksandra and Kanazir, Selma",
year = "2018",
abstract = "Dietary restriction (DR) is an important experimental paradigm for lifespan and healthspan extension, but its specific contribution regarding the type, onset, and duration are still debatable. This study was designed to examine the impact of different dietary protocols by assessing the behavioral changes during aging. We exposed male Wistar rats of various age to ad libitum (AL) or DR (60 per cent of AL daily intake) feeding regimens with different onsets. The impact of DR on locomotor activity, memory, and learning was examined in 12-, 18-, and 24-month-old treated animals and controls using open field and Y-maze tests. We have also evaluated the effects of different DR's through the quantification of animal frailty, using behavioral data to create the frailty score. Our results indicated that DR improves general animal activity and spatial memory and decreases frailty with the effect being highly dependent on DR duration and onset. Notably, life-long restriction started at young age had the most profound effect. In contrast, shorter duration and later onset of restricted diet had significantly lower or no impact on animal's behavior and frailty. This study signifies the importance of DR starting point and duration as critical determinants of DR effects on healthspan.",
journal = "The Journals of Gerontology: Series A",
title = "Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging",
number = "8",
volume = "73",
doi = "10.1093/gerona/gly015",
pages = "1036-1044"
}

Todorović, S., Smiljanić, K., Ruždijić, S., Mladenović, A.,& Kanazir, S.. (2018). Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging. in The Journals of Gerontology: Series A, 73(8), 1036-1044.
https://doi.org/10.1093/gerona/gly015

Todorović S, Smiljanić K, Ruždijić S, Mladenović A, Kanazir S. Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging. in The Journals of Gerontology: Series A. 2018;73(8):1036-1044.
doi:10.1093/gerona/gly015 .

Todorović, Smilja, Smiljanić, Kosara, Ruždijić, Sabera, Mladenović, Aleksandra, Kanazir, Selma, "Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging" in The Journals of Gerontology: Series A, 73, no. 8 (2018):1036-1044,
https://doi.org/10.1093/gerona/gly015 . .

TY  - JOUR
AU  - Smiljanić, Kosara
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
AU  - Vanmierlo, Tim
AU  - Lütjohann, Dieter
AU  - Ivković, Sanja
AU  - Kanazir, Selma
PY  - 2018
UR  - http://link.springer.com/10.1007/s10522-018-9743-y
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29340834
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2960
AB  - Albeit aging is an inevitable process, the rate of aging is susceptible to modifications. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay aging and increase healthspan in diverse species. This study aimed to compare the impact of different restricting feeding regimes such as limited daily feeding (LDF, 60% AL) and intermittent feeding (IF) on brain energy homeostasis during aging. The analysis was focused on the key molecules in glucose and cholesterol metabolism in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month-old) male Wistar rats. We measured the impact of different DRs on the expression levels of AMPK, glucose transporters (GLUT1, GLUT3, GLUT4), and the rate-limiting enzyme in the cholesterol synthesis pathway (HMGCR). Additionally, we assessed the changes in the amounts of cholesterol, its metabolite, and precursors following LDF and IF. IF decreased the levels of AMPK and pAMPK in the cortex while the increased levels were detected in the hippocampus. Glucose metabolism was more affected in the cortex, while cholesterol metabolism was more influenced in the hippocampus. Overall, the hippocampus was more resilient to the DRs, with fewer changes compared to the cortex. We showed that LDF and IF differently affected the brain energy homeostasis during aging and that specific brain regions exhibited distinct vulnerabilities towards DRs. Consequently, special attention should be paid to the DR application among elderly as different phases of aging do not respond equally to altered nutritional regimes.
T2  - Biogerontology
T1  - Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging.
IS  - 2
VL  - 19
DO  - 10.1007/s10522-018-9743-y
SP  - 121
EP  - 132
ER  - 

@article{
author = "Smiljanić, Kosara and Todorović, Smilja and Mladenović, Aleksandra and Vanmierlo, Tim and Lütjohann, Dieter and Ivković, Sanja and Kanazir, Selma",
year = "2018",
abstract = "Albeit aging is an inevitable process, the rate of aging is susceptible to modifications. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay aging and increase healthspan in diverse species. This study aimed to compare the impact of different restricting feeding regimes such as limited daily feeding (LDF, 60% AL) and intermittent feeding (IF) on brain energy homeostasis during aging. The analysis was focused on the key molecules in glucose and cholesterol metabolism in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month-old) male Wistar rats. We measured the impact of different DRs on the expression levels of AMPK, glucose transporters (GLUT1, GLUT3, GLUT4), and the rate-limiting enzyme in the cholesterol synthesis pathway (HMGCR). Additionally, we assessed the changes in the amounts of cholesterol, its metabolite, and precursors following LDF and IF. IF decreased the levels of AMPK and pAMPK in the cortex while the increased levels were detected in the hippocampus. Glucose metabolism was more affected in the cortex, while cholesterol metabolism was more influenced in the hippocampus. Overall, the hippocampus was more resilient to the DRs, with fewer changes compared to the cortex. We showed that LDF and IF differently affected the brain energy homeostasis during aging and that specific brain regions exhibited distinct vulnerabilities towards DRs. Consequently, special attention should be paid to the DR application among elderly as different phases of aging do not respond equally to altered nutritional regimes.",
journal = "Biogerontology",
title = "Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging.",
number = "2",
volume = "19",
doi = "10.1007/s10522-018-9743-y",
pages = "121-132"
}

Smiljanić, K., Todorović, S., Mladenović, A., Vanmierlo, T., Lütjohann, D., Ivković, S.,& Kanazir, S.. (2018). Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging.. in Biogerontology, 19(2), 121-132.
https://doi.org/10.1007/s10522-018-9743-y

Smiljanić K, Todorović S, Mladenović A, Vanmierlo T, Lütjohann D, Ivković S, Kanazir S. Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging.. in Biogerontology. 2018;19(2):121-132.
doi:10.1007/s10522-018-9743-y .

Smiljanić, Kosara, Todorović, Smilja, Mladenović, Aleksandra, Vanmierlo, Tim, Lütjohann, Dieter, Ivković, Sanja, Kanazir, Selma, "Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging." in Biogerontology, 19, no. 2 (2018):121-132,
https://doi.org/10.1007/s10522-018-9743-y . .

TY  - JOUR
AU  - Lavrnja, Irena
AU  - Smiljanić, Kosara
AU  - Savić, Danijela
AU  - Mladenović, Aleksandra
AU  - Milošević, Katarina
AU  - Kanazir, Selma
AU  - Peković, Sanja
PY  - 2017
UR  - http://www.nature.com/articles/s41598-017-02638-8
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2760
AB  - Increased evidence suggests that dysregulation of cholesterol metabolism may be a key event contributing to progression of multiple sclerosis (MS). Using an experimental autoimmune encephalomyelitis (EAE) model of MS we revealed specific changes in the mRNA and protein expression of key molecules involved in the maintaining of cholesterol homeostasis in the rat spinal cord: 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) during the course of disease. The presence of myelin lipid debris was seen only at the peak of EAE in demyelination loci being efficiently removed during the recovery period. Since CYP46A1 is responsible for removal of cholesterol excess, we performed a detailed profiling of CYP46A1 expression and revealed regional and temporal specificities in its distribution. Double immunofluorescence staining demonstrated CYP46A1 localization with neurons, infiltrated macrophages, microglia and astrocytes in the areas of demyelination, suggesting that these cells play a role in cholesterol turnover in EAE. We propose that alterations in the regulation of cholesterol metabolism at the onset and peak of EAE may add to the progression of disease, while during the recovery period may have beneficial effects contributing to the regeneration of myelin sheath and restoration of neuronal function.
T2  - Scientific Reports
T1  - Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord
IS  - 1
VL  - 7
DO  - 10.1038/s41598-017-02638-8
SP  - 2702
EP  - 2702
ER  - 

@article{
author = "Lavrnja, Irena and Smiljanić, Kosara and Savić, Danijela and Mladenović, Aleksandra and Milošević, Katarina and Kanazir, Selma and Peković, Sanja",
year = "2017",
abstract = "Increased evidence suggests that dysregulation of cholesterol metabolism may be a key event contributing to progression of multiple sclerosis (MS). Using an experimental autoimmune encephalomyelitis (EAE) model of MS we revealed specific changes in the mRNA and protein expression of key molecules involved in the maintaining of cholesterol homeostasis in the rat spinal cord: 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) during the course of disease. The presence of myelin lipid debris was seen only at the peak of EAE in demyelination loci being efficiently removed during the recovery period. Since CYP46A1 is responsible for removal of cholesterol excess, we performed a detailed profiling of CYP46A1 expression and revealed regional and temporal specificities in its distribution. Double immunofluorescence staining demonstrated CYP46A1 localization with neurons, infiltrated macrophages, microglia and astrocytes in the areas of demyelination, suggesting that these cells play a role in cholesterol turnover in EAE. We propose that alterations in the regulation of cholesterol metabolism at the onset and peak of EAE may add to the progression of disease, while during the recovery period may have beneficial effects contributing to the regeneration of myelin sheath and restoration of neuronal function.",
journal = "Scientific Reports",
title = "Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord",
number = "1",
volume = "7",
doi = "10.1038/s41598-017-02638-8",
pages = "2702-2702"
}

Lavrnja, I., Smiljanić, K., Savić, D., Mladenović, A., Milošević, K., Kanazir, S.,& Peković, S.. (2017). Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord. in Scientific Reports, 7(1), 2702-2702.
https://doi.org/10.1038/s41598-017-02638-8

Lavrnja I, Smiljanić K, Savić D, Mladenović A, Milošević K, Kanazir S, Peković S. Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord. in Scientific Reports. 2017;7(1):2702-2702.
doi:10.1038/s41598-017-02638-8 .

Lavrnja, Irena, Smiljanić, Kosara, Savić, Danijela, Mladenović, Aleksandra, Milošević, Katarina, Kanazir, Selma, Peković, Sanja, "Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord" in Scientific Reports, 7, no. 1 (2017):2702-2702,
https://doi.org/10.1038/s41598-017-02638-8 . .

TY  - JOUR
AU  - Smiljanić, Kosara
AU  - Mladenović, Aleksandra
AU  - Todorović, Smilja
AU  - Kanazir, Selma
PY  - 2017
UR  - https://ojs.pmf.uns.ac.rs/index.php/dbe_serbica/article/view/6492
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2817
AB  - Aging is a complex set of events that involves the whole body. However, disruption of the central nervous system (CNS) function is the aspect of aging that elderly people worry about most. Aging has different effects on different aspects of neurological function. Our knowledge of the basic molecular mechanism of brain aging has significantly improved over the past few decades. The rate of aging is not fixed, but is plastic and subject to modifications. The environmental factor proven to be very potent in modulating aging is reduced dietary intake. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay ageing and increase an active and healthy lifespan in diverse species, from yeast to mammals. Additionally, DR can improve various brain functions, including learning and memory, synaptic plasticity and neurogenesis.
T2  - Biologia Serbica
T1  - The aging brain - molecular and metabolic changes
IS  - 1
VL  - 39
DO  - 10.5281/zenodo.826613
SP  - 26
EP  - 31
ER  - 

@article{
author = "Smiljanić, Kosara and Mladenović, Aleksandra and Todorović, Smilja and Kanazir, Selma",
year = "2017",
abstract = "Aging is a complex set of events that involves the whole body. However, disruption of the central nervous system (CNS) function is the aspect of aging that elderly people worry about most. Aging has different effects on different aspects of neurological function. Our knowledge of the basic molecular mechanism of brain aging has significantly improved over the past few decades. The rate of aging is not fixed, but is plastic and subject to modifications. The environmental factor proven to be very potent in modulating aging is reduced dietary intake. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay ageing and increase an active and healthy lifespan in diverse species, from yeast to mammals. Additionally, DR can improve various brain functions, including learning and memory, synaptic plasticity and neurogenesis.",
journal = "Biologia Serbica",
title = "The aging brain - molecular and metabolic changes",
number = "1",
volume = "39",
doi = "10.5281/zenodo.826613",
pages = "26-31"
}

Smiljanić, K., Mladenović, A., Todorović, S.,& Kanazir, S.. (2017). The aging brain - molecular and metabolic changes. in Biologia Serbica, 39(1), 26-31.
https://doi.org/10.5281/zenodo.826613

Smiljanić K, Mladenović A, Todorović S, Kanazir S. The aging brain - molecular and metabolic changes. in Biologia Serbica. 2017;39(1):26-31.
doi:10.5281/zenodo.826613 .

Smiljanić, Kosara, Mladenović, Aleksandra, Todorović, Smilja, Kanazir, Selma, "The aging brain - molecular and metabolic changes" in Biologia Serbica, 39, no. 1 (2017):26-31,
https://doi.org/10.5281/zenodo.826613 . .

TY  - JOUR
AU  - Pavković, Željko
AU  - Smiljanić, Kosara
AU  - Kanazir, Selma
AU  - Milanović, Desanka
AU  - Pešić, Vesna
AU  - Ruždijić, Sabera
PY  - 2017
UR  - http://doi.wiley.com/10.1111/pan.13182
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2831
AB  - Background: Propofol is commonly used in modern anesthesiology. Some findings suggest that it is highly addictive. Aim: In this study it was examined whether propofol anesthesia exposure was able to induce behavioral alterations and brain molecular changes already described in addictive drug usage in peripubertal rats, during the onset of mid/periadolescence as a developmental period with increasing vulnerability to drug addiction. Methods: The expression of D1 dopamine receptor, a dopamine, and cAMP-regulated phosphoprotein with a Mr 32 000; Ca 2+ /calmodulin-dependent protein kinase IIα; and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B was examined in peripubertal rats 4, 24, and 48 hour after propofol anesthesia exposure by Western blot and immunohistochemistry. Brain regions of interest were the medial prefrontal cortex, the striatum, and the thalamus. Anxiety and behavioral cross-sensitization to d-amphetamine were examined as well. Results: Significant increase in the expression of dopamine and cAMP-regulated phosphoprotein with a Mr 32 000 phosphorylated at threonine 34, a postsynaptic marker of dopaminergic neurotransmission, and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B, a marker of neuronal activity, was detected in the thalamus of experimental animals 4-24 hour after the treatment, with the accent on the paraventricular thalamic nucleus. Significant increase in the expression of Ca 2+ /calmodulin-dependent protein kinase IIα phosphorylated at threonine 286, a sensor of synaptic activity, was observed in the prefrontal cortex and the striatum 24 hour after propofol anesthesia exposure. It was accompanied by a significant decrease in Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B expression in the striatum. Decreased behavioral inhibition in aversive environment and increased motor response to d-amphetamine in a context-independent manner were observed as well. Conclusion: In peripubertal rats, propofol anesthesia exposure induces transient molecular and behavioral response that share similarities with those reported previously for addictive drugs. In the absence of additional pharmacological manipulation, all detected effects receded within 48 hour after the treatment.
T2  - Pediatric Anesthesia
T1  - Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats
IS  - 9
VL  - 27
DO  - 10.1111/pan.13182
SP  - 962
EP  - 972
ER  - 

@article{
author = "Pavković, Željko and Smiljanić, Kosara and Kanazir, Selma and Milanović, Desanka and Pešić, Vesna and Ruždijić, Sabera",
year = "2017",
abstract = "Background: Propofol is commonly used in modern anesthesiology. Some findings suggest that it is highly addictive. Aim: In this study it was examined whether propofol anesthesia exposure was able to induce behavioral alterations and brain molecular changes already described in addictive drug usage in peripubertal rats, during the onset of mid/periadolescence as a developmental period with increasing vulnerability to drug addiction. Methods: The expression of D1 dopamine receptor, a dopamine, and cAMP-regulated phosphoprotein with a Mr 32 000; Ca 2+ /calmodulin-dependent protein kinase IIα; and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B was examined in peripubertal rats 4, 24, and 48 hour after propofol anesthesia exposure by Western blot and immunohistochemistry. Brain regions of interest were the medial prefrontal cortex, the striatum, and the thalamus. Anxiety and behavioral cross-sensitization to d-amphetamine were examined as well. Results: Significant increase in the expression of dopamine and cAMP-regulated phosphoprotein with a Mr 32 000 phosphorylated at threonine 34, a postsynaptic marker of dopaminergic neurotransmission, and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B, a marker of neuronal activity, was detected in the thalamus of experimental animals 4-24 hour after the treatment, with the accent on the paraventricular thalamic nucleus. Significant increase in the expression of Ca 2+ /calmodulin-dependent protein kinase IIα phosphorylated at threonine 286, a sensor of synaptic activity, was observed in the prefrontal cortex and the striatum 24 hour after propofol anesthesia exposure. It was accompanied by a significant decrease in Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B expression in the striatum. Decreased behavioral inhibition in aversive environment and increased motor response to d-amphetamine in a context-independent manner were observed as well. Conclusion: In peripubertal rats, propofol anesthesia exposure induces transient molecular and behavioral response that share similarities with those reported previously for addictive drugs. In the absence of additional pharmacological manipulation, all detected effects receded within 48 hour after the treatment.",
journal = "Pediatric Anesthesia",
title = "Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats",
number = "9",
volume = "27",
doi = "10.1111/pan.13182",
pages = "962-972"
}

Pavković, Ž., Smiljanić, K., Kanazir, S., Milanović, D., Pešić, V.,& Ruždijić, S.. (2017). Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats. in Pediatric Anesthesia, 27(9), 962-972.
https://doi.org/10.1111/pan.13182

Pavković Ž, Smiljanić K, Kanazir S, Milanović D, Pešić V, Ruždijić S. Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats. in Pediatric Anesthesia. 2017;27(9):962-972.
doi:10.1111/pan.13182 .

Pavković, Željko, Smiljanić, Kosara, Kanazir, Selma, Milanović, Desanka, Pešić, Vesna, Ruždijić, Sabera, "Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats" in Pediatric Anesthesia, 27, no. 9 (2017):962-972,
https://doi.org/10.1111/pan.13182 . .

TY  - JOUR
AU  - Cermak, Stjepko
AU  - Kosicek, Marko
AU  - Mladenović, Aleksandra
AU  - Smiljanić, Kosara
AU  - Kanazir, Selma
AU  - Hecimovic, Silva
AU  - Lakshmana, Madepalli K.
PY  - 2016
UR  - https://www.scopus.com/record/display.uri?eid=2-s2.0-84999143646&origin=SingleRecordEmailAlert&dgcid=scalert_sc_search_email&txGid=BC81928C1802E221B1A9A8D8F9963BDB.wsnAw8kcdt7IPYLO0V48gA%253a21
UR  - http://dx.plos.org/10.1371/journal.pone.0167428
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2478
AB  - Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment of lysosomal function plays an important role in neuronal degeneration and in the pathogenesis of numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss of the major lysosomal proteases, the cysteine cathepsins B and L (CtsB/L), affects lysosomal function, cholesterol metabolism and degradation of the key Alzheimer's disease (AD) proteins. Here, we show that cysteine CtsB/L, and not the aspartyl cathepsin D (CtsD), represent a major lysosomal protease(s) that control lysosomal function, intracellular cholesterol trafficking and AD-like amyloidogenic features. Intriguingly, accumulation of free cholesterol in late endosomes/lysosomes upon CtsB/L inhibition resembled a phenotype characteristic for the rare neurodegenerative disorder Niemann-Pick type C (NPC). CtsB/L inhibition and not the inhibition of CtsD led to lysosomal impairment assessed by decreased degradation of EGF receptor, enhanced LysoTracker staining and accumulation of several lysosomal proteins LC3II, NPC1 and NPC2. By measuring the levels of NPC1 and ABCA1, the two major cholesterol efflux proteins, we showed that CtsB/L inhibition or genetic depletion caused accumulation of the NPC1 in lysosomes and downregulation of ABCA1 protein levels and its expression. Furthermore, we revealed that CtsB/L are involved in degradation of the key Alzheimer’s proteins: amyloid-β peptides (Aβ) and C-terminal fragments of the amyloid precursor protein (APP) and in degradation of β-secretase (BACE1). Our results imply CtsB/L as major regulators of lysosomal function and demonstrate that CtsB/L may play an important role in intracellular cholesterol trafficking and in degradation of the key AD proteins. Our findings implicate that enhancing the activity or levels of CtsB/L could provide a promising and a common strategy for maintaining lysosomal function and for preventing and/or treating neurodegenerative diseases.
T2  - PLOS ONE
T1  - Loss of Cathepsin B and L Leads to Lysosomal Dysfunction, NPC-Like Cholesterol Sequestration and Accumulation of the Key Alzheimer's Proteins
IS  - 11
VL  - 11
DO  - 10.1371/journal.pone.0167428
SP  - e0167428
EP  - e0167428
ER  - 

@article{
author = "Cermak, Stjepko and Kosicek, Marko and Mladenović, Aleksandra and Smiljanić, Kosara and Kanazir, Selma and Hecimovic, Silva and Lakshmana, Madepalli K.",
year = "2016",
abstract = "Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment of lysosomal function plays an important role in neuronal degeneration and in the pathogenesis of numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss of the major lysosomal proteases, the cysteine cathepsins B and L (CtsB/L), affects lysosomal function, cholesterol metabolism and degradation of the key Alzheimer's disease (AD) proteins. Here, we show that cysteine CtsB/L, and not the aspartyl cathepsin D (CtsD), represent a major lysosomal protease(s) that control lysosomal function, intracellular cholesterol trafficking and AD-like amyloidogenic features. Intriguingly, accumulation of free cholesterol in late endosomes/lysosomes upon CtsB/L inhibition resembled a phenotype characteristic for the rare neurodegenerative disorder Niemann-Pick type C (NPC). CtsB/L inhibition and not the inhibition of CtsD led to lysosomal impairment assessed by decreased degradation of EGF receptor, enhanced LysoTracker staining and accumulation of several lysosomal proteins LC3II, NPC1 and NPC2. By measuring the levels of NPC1 and ABCA1, the two major cholesterol efflux proteins, we showed that CtsB/L inhibition or genetic depletion caused accumulation of the NPC1 in lysosomes and downregulation of ABCA1 protein levels and its expression. Furthermore, we revealed that CtsB/L are involved in degradation of the key Alzheimer’s proteins: amyloid-β peptides (Aβ) and C-terminal fragments of the amyloid precursor protein (APP) and in degradation of β-secretase (BACE1). Our results imply CtsB/L as major regulators of lysosomal function and demonstrate that CtsB/L may play an important role in intracellular cholesterol trafficking and in degradation of the key AD proteins. Our findings implicate that enhancing the activity or levels of CtsB/L could provide a promising and a common strategy for maintaining lysosomal function and for preventing and/or treating neurodegenerative diseases.",
journal = "PLOS ONE",
title = "Loss of Cathepsin B and L Leads to Lysosomal Dysfunction, NPC-Like Cholesterol Sequestration and Accumulation of the Key Alzheimer's Proteins",
number = "11",
volume = "11",
doi = "10.1371/journal.pone.0167428",
pages = "e0167428-e0167428"
}

Cermak, S., Kosicek, M., Mladenović, A., Smiljanić, K., Kanazir, S., Hecimovic, S.,& Lakshmana, M. K.. (2016). Loss of Cathepsin B and L Leads to Lysosomal Dysfunction, NPC-Like Cholesterol Sequestration and Accumulation of the Key Alzheimer's Proteins. in PLOS ONE, 11(11), e0167428-e0167428.
https://doi.org/10.1371/journal.pone.0167428

Cermak S, Kosicek M, Mladenović A, Smiljanić K, Kanazir S, Hecimovic S, Lakshmana MK. Loss of Cathepsin B and L Leads to Lysosomal Dysfunction, NPC-Like Cholesterol Sequestration and Accumulation of the Key Alzheimer's Proteins. in PLOS ONE. 2016;11(11):e0167428-e0167428.
doi:10.1371/journal.pone.0167428 .

Cermak, Stjepko, Kosicek, Marko, Mladenović, Aleksandra, Smiljanić, Kosara, Kanazir, Selma, Hecimovic, Silva, Lakshmana, Madepalli K., "Loss of Cathepsin B and L Leads to Lysosomal Dysfunction, NPC-Like Cholesterol Sequestration and Accumulation of the Key Alzheimer's Proteins" in PLOS ONE, 11, no. 11 (2016):e0167428-e0167428,
https://doi.org/10.1371/journal.pone.0167428 . .

TY  - JOUR
AU  - Smiljanić, Kosara
AU  - Pesic, Vesna
AU  - Mladenović, Aleksandra
AU  - Pavković, Željko
AU  - Brkić, Marjana
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2013
AB  - Dietary restriction (DR) exerts significant beneficial effects in terms
   of aging and age-related diseases in many organisms including humans.
   The present study aimed to examine the influence of long-term DR on the
   BDNF system at the transcriptional and translational levels in the
   cortex and hippocampus of middle-aged (12-month-old) and aged
   (24-month-old) male Wistar rats. The obtained results revealed that the
   DR upregulated the expression of exon-specific BDNF transcripts in both
   regions, followed by elevated levels of mBDNF only in the cortex in
   middle-aged animals. In aged animals, DR modulated BDNF protein levels
   by increasing proBDNF and by declining mBDNF levels. Additionally,
   elevated levels of the full-length TrkB accompanied by a decreased level
   of the less-glycosylated TrkB protein were observed in middle-aged rats
   following DR, while in aged rats, DR amplified only the expression of
   the less-glycosylated form of TrkB. The levels of phosphorylated
   TrkB(Y816) were stable during aging regardless of feeding. Reduced
   levels of p75(NTR) were detected in both regions of middle-aged DR-fed
   animals, while a significant increase was measured in the cortex of aged
   DR-fed rats. These findings shed additional light on DR as a modulator
   of BDNF system revealing its disparate effects in middle-aged and aged
   animals. Given the importance of the proBDNF/BDNF circuit-level
   expression in different brain functions and various aspects of behavior,
   it is necessary to further elucidate the optimal duration of the applied
   dietary regimen with regard to the animal age in order to achieve its
   most favorable effects.
T2  - Biogerontology
T1  - Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats
IS  - 1
VL  - 16
DO  - 10.1007/s10522-014-9537-9
SP  - 71
EP  - 83
ER  - 

@article{
author = "Smiljanić, Kosara and Pesic, Vesna and Mladenović, Aleksandra and Pavković, Željko and Brkić, Marjana and Ruždijić, Sabera and Kanazir, Selma",
year = "2015",
abstract = "Dietary restriction (DR) exerts significant beneficial effects in terms
   of aging and age-related diseases in many organisms including humans.
   The present study aimed to examine the influence of long-term DR on the
   BDNF system at the transcriptional and translational levels in the
   cortex and hippocampus of middle-aged (12-month-old) and aged
   (24-month-old) male Wistar rats. The obtained results revealed that the
   DR upregulated the expression of exon-specific BDNF transcripts in both
   regions, followed by elevated levels of mBDNF only in the cortex in
   middle-aged animals. In aged animals, DR modulated BDNF protein levels
   by increasing proBDNF and by declining mBDNF levels. Additionally,
   elevated levels of the full-length TrkB accompanied by a decreased level
   of the less-glycosylated TrkB protein were observed in middle-aged rats
   following DR, while in aged rats, DR amplified only the expression of
   the less-glycosylated form of TrkB. The levels of phosphorylated
   TrkB(Y816) were stable during aging regardless of feeding. Reduced
   levels of p75(NTR) were detected in both regions of middle-aged DR-fed
   animals, while a significant increase was measured in the cortex of aged
   DR-fed rats. These findings shed additional light on DR as a modulator
   of BDNF system revealing its disparate effects in middle-aged and aged
   animals. Given the importance of the proBDNF/BDNF circuit-level
   expression in different brain functions and various aspects of behavior,
   it is necessary to further elucidate the optimal duration of the applied
   dietary regimen with regard to the animal age in order to achieve its
   most favorable effects.",
journal = "Biogerontology",
title = "Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats",
number = "1",
volume = "16",
doi = "10.1007/s10522-014-9537-9",
pages = "71-83"
}

Smiljanić, K., Pesic, V., Mladenović, A., Pavković, Ž., Brkić, M., Ruždijić, S.,& Kanazir, S.. (2015). Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats. in Biogerontology, 16(1), 71-83.
https://doi.org/10.1007/s10522-014-9537-9

Smiljanić K, Pesic V, Mladenović A, Pavković Ž, Brkić M, Ruždijić S, Kanazir S. Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats. in Biogerontology. 2015;16(1):71-83.
doi:10.1007/s10522-014-9537-9 .

Smiljanić, Kosara, Pesic, Vesna, Mladenović, Aleksandra, Pavković, Željko, Brkić, Marjana, Ruždijić, Sabera, Kanazir, Selma, "Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats" in Biogerontology, 16, no. 1 (2015):71-83,
https://doi.org/10.1007/s10522-014-9537-9 . .

TY  - JOUR
AU  - Tesic, Vesna
AU  - Perovic, Milka
AU  - Lazic, Divna
AU  - Kojic, Snezana
AU  - Smiljanić, Kosara
AU  - Ruždijić, Sabera
AU  - Rakic, Ljubisav
AU  - Kanazir, Selma
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1967
AB  - Diminished glucocorticoid signaling is associated with an age-related
   decline in hippocampal functioning. In this study we demonstrate the
   effect of intermittent, every other day (EOD) feeding on the
   glucocorticoid hormone/glucocorticoid receptor (GR) system in the
   hippocampus of middle-aged (18-month-old) and aged (24-month-old) Wistar
   rats. In aged ad libitum-fed rats, a decrease in the level of total GR
   and GR phosphorylated at Ser(232) (pGR) was detected. Conversely, aged
   rats subjected to EOD feeding, starting from 6 months of age, showed an
   increase in GR and pGR levels and a higher content of hippocampal
   corticosterone. Furthermore, prominent nuclear staining of pGR was
   observed in CM pyramidal and DG granule neurons of aged EOD-fed rats.
   These changes were accompanied by increased Sglc-1 and decreased GFAP
   transcription, pointing to upregulated transcriptional activity of GR.
   EOD feeding also induced an increase in the expression of the
   mineralocorticoid receptor. Our results reveal that intermittent feeding
   restores impaired GR signaling in the hippocampus of aged animals by
   inducing rather than by stabilizing GR signaling during aging. (C) 2015
   Elsevier Ltd. All rights reserved.
T2  - Journal of Steroid Biochemistry and Molecular Biology
T1  - Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat
VL  - 149
DO  - 10.1016/j.jsbmb.2015.01.013
SP  - 43
EP  - 52
ER  - 

@article{
author = "Tesic, Vesna and Perovic, Milka and Lazic, Divna and Kojic, Snezana and Smiljanić, Kosara and Ruždijić, Sabera and Rakic, Ljubisav and Kanazir, Selma",
year = "2015",
abstract = "Diminished glucocorticoid signaling is associated with an age-related
   decline in hippocampal functioning. In this study we demonstrate the
   effect of intermittent, every other day (EOD) feeding on the
   glucocorticoid hormone/glucocorticoid receptor (GR) system in the
   hippocampus of middle-aged (18-month-old) and aged (24-month-old) Wistar
   rats. In aged ad libitum-fed rats, a decrease in the level of total GR
   and GR phosphorylated at Ser(232) (pGR) was detected. Conversely, aged
   rats subjected to EOD feeding, starting from 6 months of age, showed an
   increase in GR and pGR levels and a higher content of hippocampal
   corticosterone. Furthermore, prominent nuclear staining of pGR was
   observed in CM pyramidal and DG granule neurons of aged EOD-fed rats.
   These changes were accompanied by increased Sglc-1 and decreased GFAP
   transcription, pointing to upregulated transcriptional activity of GR.
   EOD feeding also induced an increase in the expression of the
   mineralocorticoid receptor. Our results reveal that intermittent feeding
   restores impaired GR signaling in the hippocampus of aged animals by
   inducing rather than by stabilizing GR signaling during aging. (C) 2015
   Elsevier Ltd. All rights reserved.",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
title = "Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat",
volume = "149",
doi = "10.1016/j.jsbmb.2015.01.013",
pages = "43-52"
}

Tesic, V., Perovic, M., Lazic, D., Kojic, S., Smiljanić, K., Ruždijić, S., Rakic, L.,& Kanazir, S.. (2015). Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat. in Journal of Steroid Biochemistry and Molecular Biology, 149, 43-52.
https://doi.org/10.1016/j.jsbmb.2015.01.013

Tesic V, Perovic M, Lazic D, Kojic S, Smiljanić K, Ruždijić S, Rakic L, Kanazir S. Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat. in Journal of Steroid Biochemistry and Molecular Biology. 2015;149:43-52.
doi:10.1016/j.jsbmb.2015.01.013 .

Tesic, Vesna, Perovic, Milka, Lazic, Divna, Kojic, Snezana, Smiljanić, Kosara, Ruždijić, Sabera, Rakic, Ljubisav, Kanazir, Selma, "Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat" in Journal of Steroid Biochemistry and Molecular Biology, 149 (2015):43-52,
https://doi.org/10.1016/j.jsbmb.2015.01.013 . .

TY  - JOUR
AU  - Mladenović, Aleksandra
AU  - Perovic, Milka
AU  - Smiljanić, Kosara
AU  - Todorovic, Smilja
AU  - Tesic, Vesna
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2223
AB  - The objective of this study was to examine the effects of aging and
   long-term dietary restriction (DR) on the level of amyloid precursor
   protein (APP) and presenilin-1 (PS-1), proteins that are critically
   involved in Alzheimer's disease. Changes in mRNA and protein expression
   were assessed by real-time PCR and western blot analysis during aging
   and long-term DR in the cortex and hippocampus of 6-, 12-, 18-, and
   24-month-old rats. Prominent regional changes in expression were
   observed in response to aging and DR. Although the hippocampus displayed
   significant alterations in APP mRNA and protein expression and no
   significant changes in PS-1 expression, an opposite pattern was observed
   in the cortex. DR counteracted the age-related changes in APP mRNA
   expression in both structures of old animals. The observed DR-induced
   increase in mRNA levels in the hippocampus was accompanied by an
   increase in the level of full-length protein APP. These results indicate
   that although both structures are very sensitive to aging, a specific
   spatial pattern of changes in APP and PS-1 occurs during aging.
   Furthermore, these findings provide evidence that DR can affect APP and
   PS-1 expression in a manner consistent with its proposed `antiaging'
   effect.
T2  - Neuroreport
T1  - The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain
IS  - 6
VL  - 25
DO  - 10.1097/WNR.0000000000000107
SP  - 398
EP  - 403
ER  - 

@article{
author = "Mladenović, Aleksandra and Perovic, Milka and Smiljanić, Kosara and Todorovic, Smilja and Tesic, Vesna and Ruždijić, Sabera and Kanazir, Selma",
year = "2014",
abstract = "The objective of this study was to examine the effects of aging and
   long-term dietary restriction (DR) on the level of amyloid precursor
   protein (APP) and presenilin-1 (PS-1), proteins that are critically
   involved in Alzheimer's disease. Changes in mRNA and protein expression
   were assessed by real-time PCR and western blot analysis during aging
   and long-term DR in the cortex and hippocampus of 6-, 12-, 18-, and
   24-month-old rats. Prominent regional changes in expression were
   observed in response to aging and DR. Although the hippocampus displayed
   significant alterations in APP mRNA and protein expression and no
   significant changes in PS-1 expression, an opposite pattern was observed
   in the cortex. DR counteracted the age-related changes in APP mRNA
   expression in both structures of old animals. The observed DR-induced
   increase in mRNA levels in the hippocampus was accompanied by an
   increase in the level of full-length protein APP. These results indicate
   that although both structures are very sensitive to aging, a specific
   spatial pattern of changes in APP and PS-1 occurs during aging.
   Furthermore, these findings provide evidence that DR can affect APP and
   PS-1 expression in a manner consistent with its proposed `antiaging'
   effect.",
journal = "Neuroreport",
title = "The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain",
number = "6",
volume = "25",
doi = "10.1097/WNR.0000000000000107",
pages = "398-403"
}

Mladenović, A., Perovic, M., Smiljanić, K., Todorovic, S., Tesic, V., Ruždijić, S.,& Kanazir, S.. (2014). The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain. in Neuroreport, 25(6), 398-403.
https://doi.org/10.1097/WNR.0000000000000107

Mladenović A, Perovic M, Smiljanić K, Todorovic S, Tesic V, Ruždijić S, Kanazir S. The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain. in Neuroreport. 2014;25(6):398-403.
doi:10.1097/WNR.0000000000000107 .

Mladenović, Aleksandra, Perovic, Milka, Smiljanić, Kosara, Todorovic, Smilja, Tesic, Vesna, Ruždijić, Sabera, Kanazir, Selma, "The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain" in Neuroreport, 25, no. 6 (2014):398-403,
https://doi.org/10.1097/WNR.0000000000000107 . .

TY  - JOUR
AU  - Perović, Milka
AU  - Tesić, Vesna T
AU  - Mladenović, Aleksandra
AU  - Smiljanić, Kosara
AU  - Lončarević-Vasiljković, Nataša
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/946
AB  - Neurotrophins are established molecular mediators of neuronal plasticity in the adult brain. We analyzed the impact of aging on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protein isoforms, their receptors, and on the expression patterns of multiple 5' exon-specific BDNF transcripts in the rat cortex and hippocampus throughout the life span of the rat (6, 12, 18, and 24 months of age). ProNGF was increased during aging in both structures. Mature NGF gradually decreased in the cortex, and, in 24-month-old animals, it was 30 % lower than that in adult 6-month-old rats. The BDNF expression did not change during aging, while proBDNF accumulated in the hippocampus of aged rats. Hippocampal total BDNF mRNA was lower in 12-month-old animals, mostly as a result of a decrease of BDNF transcripts 1 and 2. In contrast to the region-specific regulation of specific exon-containing BDNF mRNAs in adult animals, the same BDNF RNA isoforms (containing exons III, IV, or VI) were present in both brain structures of aged animals. Deficits in neurotrophin signaling were supported by the observed decrease in Trk receptor expression which was accompanied by lower levels of the two main downstream effector kinases, pAkt and protein kinase C. The proteolytic processing of p75NTR observed in 12-month-old rats points to an additional regulatory mechanism in early aging. The changes described herein could contribute to reduced brain plasticity underlying the age-dependent decline in cognitive function.
T2  - Age
T1  - BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat
IS  - 6
VL  - 35
SP  - 233
EP  - 2070
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_946
ER  - 

@article{
author = "Perović, Milka and Tesić, Vesna T and Mladenović, Aleksandra and Smiljanić, Kosara and Lončarević-Vasiljković, Nataša and Ruždijić, Sabera and Kanazir, Selma",
year = "2013",
abstract = "Neurotrophins are established molecular mediators of neuronal plasticity in the adult brain. We analyzed the impact of aging on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protein isoforms, their receptors, and on the expression patterns of multiple 5' exon-specific BDNF transcripts in the rat cortex and hippocampus throughout the life span of the rat (6, 12, 18, and 24 months of age). ProNGF was increased during aging in both structures. Mature NGF gradually decreased in the cortex, and, in 24-month-old animals, it was 30 % lower than that in adult 6-month-old rats. The BDNF expression did not change during aging, while proBDNF accumulated in the hippocampus of aged rats. Hippocampal total BDNF mRNA was lower in 12-month-old animals, mostly as a result of a decrease of BDNF transcripts 1 and 2. In contrast to the region-specific regulation of specific exon-containing BDNF mRNAs in adult animals, the same BDNF RNA isoforms (containing exons III, IV, or VI) were present in both brain structures of aged animals. Deficits in neurotrophin signaling were supported by the observed decrease in Trk receptor expression which was accompanied by lower levels of the two main downstream effector kinases, pAkt and protein kinase C. The proteolytic processing of p75NTR observed in 12-month-old rats points to an additional regulatory mechanism in early aging. The changes described herein could contribute to reduced brain plasticity underlying the age-dependent decline in cognitive function.",
journal = "Age",
title = "BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat",
number = "6",
volume = "35",
pages = "233-2070",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_946"
}

Perović, M., Tesić, V. T., Mladenović, A., Smiljanić, K., Lončarević-Vasiljković, N., Ruždijić, S.,& Kanazir, S.. (2013). BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. in Age, 35(6), 233-2070.
https://hdl.handle.net/21.15107/rcub_ibiss_946

Perović M, Tesić VT, Mladenović A, Smiljanić K, Lončarević-Vasiljković N, Ruždijić S, Kanazir S. BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. in Age. 2013;35(6):233-2070.
https://hdl.handle.net/21.15107/rcub_ibiss_946 .

Perović, Milka, Tesić, Vesna T, Mladenović, Aleksandra, Smiljanić, Kosara, Lončarević-Vasiljković, Nataša, Ruždijić, Sabera, Kanazir, Selma, "BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat" in Age, 35, no. 6 (2013):233-2070,
https://hdl.handle.net/21.15107/rcub_ibiss_946 .

TY  - JOUR
AU  - Smiljanić, Kosara
AU  - Vanmierlo, Tim
AU  - Mladenović, Aleksandra
AU  - Perović, Milka
AU  - Lončarević-Vasiljković, Nataša
AU  - Tesić, Vesna T
AU  - Rakić, Ljubisav
AU  - Ruždijić, Sabera
AU  - Lutjohann, Dieter
AU  - Kanazir, Selma
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/953
AB  - Disturbance of cholesterol homeostasis in the brain is coupled to age-related brain dysfunction. In the present work, we studied the relationship between aging and cholesterol metabolism in two brain regions, the cortex and hippocampus, as well as in the sera and liver of 6-, 12-, 18- and 24-month-old male Wistar rats. Using gas chromatography-mass spectrometry, we undertook a comparative analysis of the concentrations of cholesterol, its precursors and metabolites, as well as dietary-derived phytosterols. During aging, the concentrations of the three cholesterol precursors examined (lanosterol, lathosterol and desmosterol) were unchanged in the cortex, except for desmosterol which decreased (44 %) in 18-month-old rats. In the hippocampus, aging was associated with a significant reduction in lanosterol and lathosterol concentrations at 24 months (28 and 25 %, respectively), as well as by a significant decrease of desmosterol concentration at 18 and 24 months (36 and 51 %, respectively). In contrast, in the liver we detected age-induced increases in lanosterol and lathosterol concentrations, and no change in desmosterol concentration. The amounts of these sterols were lower than in the brain regions. In the cortex and hippocampus, desmosterol was the predominant cholesterol precursor. In the liver, lathosterol was the most abundant precursor. This ratio remained stable during aging. The most striking effect of aging observed in our study was a significant decrease in desmosterol concentration in the hippocampus which could reflect age-related reduced synaptic plasticity, thus representing one of the detrimental effects of advanced age.
T2  - Lipids
T1  - Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver
IS  - 11
VL  - 48
SP  - 5
EP  - 1077
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_953
ER  - 

@article{
author = "Smiljanić, Kosara and Vanmierlo, Tim and Mladenović, Aleksandra and Perović, Milka and Lončarević-Vasiljković, Nataša and Tesić, Vesna T and Rakić, Ljubisav and Ruždijić, Sabera and Lutjohann, Dieter and Kanazir, Selma",
year = "2013",
abstract = "Disturbance of cholesterol homeostasis in the brain is coupled to age-related brain dysfunction. In the present work, we studied the relationship between aging and cholesterol metabolism in two brain regions, the cortex and hippocampus, as well as in the sera and liver of 6-, 12-, 18- and 24-month-old male Wistar rats. Using gas chromatography-mass spectrometry, we undertook a comparative analysis of the concentrations of cholesterol, its precursors and metabolites, as well as dietary-derived phytosterols. During aging, the concentrations of the three cholesterol precursors examined (lanosterol, lathosterol and desmosterol) were unchanged in the cortex, except for desmosterol which decreased (44 %) in 18-month-old rats. In the hippocampus, aging was associated with a significant reduction in lanosterol and lathosterol concentrations at 24 months (28 and 25 %, respectively), as well as by a significant decrease of desmosterol concentration at 18 and 24 months (36 and 51 %, respectively). In contrast, in the liver we detected age-induced increases in lanosterol and lathosterol concentrations, and no change in desmosterol concentration. The amounts of these sterols were lower than in the brain regions. In the cortex and hippocampus, desmosterol was the predominant cholesterol precursor. In the liver, lathosterol was the most abundant precursor. This ratio remained stable during aging. The most striking effect of aging observed in our study was a significant decrease in desmosterol concentration in the hippocampus which could reflect age-related reduced synaptic plasticity, thus representing one of the detrimental effects of advanced age.",
journal = "Lipids",
title = "Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver",
number = "11",
volume = "48",
pages = "5-1077",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_953"
}

Smiljanić, K., Vanmierlo, T., Mladenović, A., Perović, M., Lončarević-Vasiljković, N., Tesić, V. T., Rakić, L., Ruždijić, S., Lutjohann, D.,& Kanazir, S.. (2013). Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver. in Lipids, 48(11), 5-1077.
https://hdl.handle.net/21.15107/rcub_ibiss_953

Smiljanić K, Vanmierlo T, Mladenović A, Perović M, Lončarević-Vasiljković N, Tesić VT, Rakić L, Ruždijić S, Lutjohann D, Kanazir S. Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver. in Lipids. 2013;48(11):5-1077.
https://hdl.handle.net/21.15107/rcub_ibiss_953 .

Smiljanić, Kosara, Vanmierlo, Tim, Mladenović, Aleksandra, Perović, Milka, Lončarević-Vasiljković, Nataša, Tesić, Vesna T, Rakić, Ljubisav, Ruždijić, Sabera, Lutjohann, Dieter, Kanazir, Selma, "Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver" in Lipids, 48, no. 11 (2013):5-1077,
https://hdl.handle.net/21.15107/rcub_ibiss_953 .

TY  - JOUR
AU  - Lončarević-Vasiljković, Nataša
AU  - Pešić, Vesna
AU  - Todorović, Smilja
AU  - Popić, Jelena
AU  - Smiljanić, Kosara
AU  - Milanović, Desanka
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4134
AB  - Traumatic brain injury (TBI) is a widespread cause of death and a major source of adult disability. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. One of the hallmarks of the secondary injury process is microglial activation resulting in increased cytokine production. Notwithstanding that recent studies demonstrated that caloric restriction (CR) lasting several months prior to an acute TBI exhibits neuroprotective properties, understanding how exactly CR influences secondary injury is still unclear. The goal of the present study was to examine whether CR (50% of daily food intake for 3 months) alleviates the effects of secondary injury on neuronal loss following cortical stab injury (CSI). To this end, we examined the effects of CR on the microglial activation, tumor necrosis factor-α (TNF-α) and caspase-3 expression in the ipsilateral (injured) cortex of the adult rats during the recovery period (from 2 to 28 days) after injury. Our results demonstrate that CR prior to CSI suppresses microglial activation, induction of TNF-α and caspase-3, as well as neurodegeneration following injury. These results indicate that CR strongly attenuates the effects of secondary injury, thus suggesting that CR may increase the successful outcome following TBI.
PB  - San Francisco:the Public Library of Science (PLOS)
T2  - PLoS One
T1  - Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats
IS  - 5
VL  - 7
DO  - 10.1371/journal.pone.0037215
SP  - e37215
ER  - 

@article{
author = "Lončarević-Vasiljković, Nataša and Pešić, Vesna and Todorović, Smilja and Popić, Jelena and Smiljanić, Kosara and Milanović, Desanka and Ruždijić, Sabera and Kanazir, Selma",
year = "2012",
abstract = "Traumatic brain injury (TBI) is a widespread cause of death and a major source of adult disability. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. One of the hallmarks of the secondary injury process is microglial activation resulting in increased cytokine production. Notwithstanding that recent studies demonstrated that caloric restriction (CR) lasting several months prior to an acute TBI exhibits neuroprotective properties, understanding how exactly CR influences secondary injury is still unclear. The goal of the present study was to examine whether CR (50% of daily food intake for 3 months) alleviates the effects of secondary injury on neuronal loss following cortical stab injury (CSI). To this end, we examined the effects of CR on the microglial activation, tumor necrosis factor-α (TNF-α) and caspase-3 expression in the ipsilateral (injured) cortex of the adult rats during the recovery period (from 2 to 28 days) after injury. Our results demonstrate that CR prior to CSI suppresses microglial activation, induction of TNF-α and caspase-3, as well as neurodegeneration following injury. These results indicate that CR strongly attenuates the effects of secondary injury, thus suggesting that CR may increase the successful outcome following TBI.",
publisher = "San Francisco:the Public Library of Science (PLOS)",
journal = "PLoS One",
title = "Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats",
number = "5",
volume = "7",
doi = "10.1371/journal.pone.0037215",
pages = "e37215"
}

Lončarević-Vasiljković, N., Pešić, V., Todorović, S., Popić, J., Smiljanić, K., Milanović, D., Ruždijić, S.,& Kanazir, S.. (2012). Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats. in PLoS One
San Francisco:the Public Library of Science (PLOS)., 7(5), e37215.
https://doi.org/10.1371/journal.pone.0037215

Lončarević-Vasiljković N, Pešić V, Todorović S, Popić J, Smiljanić K, Milanović D, Ruždijić S, Kanazir S. Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats. in PLoS One. 2012;7(5):e37215.
doi:10.1371/journal.pone.0037215 .

Lončarević-Vasiljković, Nataša, Pešić, Vesna, Todorović, Smilja, Popić, Jelena, Smiljanić, Kosara, Milanović, Desanka, Ruždijić, Sabera, Kanazir, Selma, "Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats" in PLoS One, 7, no. 5 (2012):e37215,
https://doi.org/10.1371/journal.pone.0037215 . .

TY  - THES
AU  - Smiljanić, Kosara
PY  - 2012
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=27
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:2272/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=41541647
UR  - http://nardus.mpn.gov.rs/123456789/2017
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2419
AB  - Starenje centralnog nervnog sistema (CNS) praćeno je brojnim promenama koje dovode do narušavanja nervnih funkcija, pre svega kontrole motorike i kognitivnih sposobnosti. Smatra se da su kognitivni poremećaji tokom starenja posledica smanjene sinaptičke plastičnosti, naročito u korteksu i hipokampusu, regionima mozga izuzetno važnim za procese učenja i pamćenja. Najvažniji faktor sredine kojim se može uticati na starenje uopšte, a samim tim i na starenje mozga je režim redukovane ishrane, bez pothranjenosti. Pored toga što se već nekoliko decenija zna da redukovana ishrana produžava životni vek mnogih vrsta, uključujući i sisare, pokazano je da ona odlaže i ublažava starosno zavisne promene u nervnom sistemu. Holesterol je najzastupljeniji lipid u ćelijama sisara. Učestvujući u izgradnji fosfolipidnog dvosloja bioloških mambrana, on reguliše njihovu fluidnost, propustljivost i rigidnost, a samim tim i funkcionalna svojstva membranskih proteina, poput jonskih kanala i transmiterskih receptora. Metabolizam holesterola predstavlja važan aspekt sinaptičke plastičnosti, jer je pokazano da je holesterol neophodan za biogenezu i transport sinaptičkih vezikula, kao i za prvilnu funkcionalnu organizaciju lipidnih ostvaca. Od svih organa u telu, mozak sadrži najviše holesterola. Održavanje homeostaze holesterola neophodno je za normalno i neometano funkcionisanje CNS...
AB  - Ageing of the central nervous system is associated with a number of changes that disturb nerve function, especially motor control and cognitive abilities. It is believed that cognitive disorders in aging are consequence of reduced synaptic plasticity, especially in the cortex and hippocampus, brain regions extremely important for learning and memory processes. Dominant factor that can influence aging in general, and therefore the aging of the brain is reduced diet regime, without malnutrition. In addition to being known for decades that reduced caloric intake prolongs life span of many species, including mammals, it is shown that it delays and alleviates age-dependent changes.Cholesterol is the most abundant lipid in mammalian cells. By participating in the construction of phospholipid bilayer of biological membranes, it regulates their fluidity, permeability and rigidity, and consequently the functional properties of membrane proteins, such as ion channels and transmmitters receptors. Cholesterol metabolism represents one aspect of synaptic plasticity, as has been shown that cholesterol is essential for biogenesis of synaptic vesicles, and vesicle transport, as well as for proper functional organization of lipid rafts. The brain contains the most cholesterol of all the organs in the body. Maintenance of cholesterol homeostasis is essential for proper functioning of the central nervous system...
PB  - Belgrade: Faculty of Biology, University of Belgrade
T2  - Faculty of Biology, University of Belgrade
T1  - Uticaj starenja i dugotrajne dijetalne restrikcije na metabolizam holesterola u prednjem mozgu pacova
T1  - Effects of aging and long-term dietary restrictions on cholesterol metabolism in the rat forebrain
DO  - 10.2298/BG20120709SMILJANIC
SP  - 1
EP  - 128
UR  - https://hdl.handle.net/21.15107/rcub_nardus_2017
ER  - 

@phdthesis{
author = "Smiljanić, Kosara",
year = "2012",
abstract = "Starenje centralnog nervnog sistema (CNS) praćeno je brojnim promenama koje dovode do narušavanja nervnih funkcija, pre svega kontrole motorike i kognitivnih sposobnosti. Smatra se da su kognitivni poremećaji tokom starenja posledica smanjene sinaptičke plastičnosti, naročito u korteksu i hipokampusu, regionima mozga izuzetno važnim za procese učenja i pamćenja. Najvažniji faktor sredine kojim se može uticati na starenje uopšte, a samim tim i na starenje mozga je režim redukovane ishrane, bez pothranjenosti. Pored toga što se već nekoliko decenija zna da redukovana ishrana produžava životni vek mnogih vrsta, uključujući i sisare, pokazano je da ona odlaže i ublažava starosno zavisne promene u nervnom sistemu. Holesterol je najzastupljeniji lipid u ćelijama sisara. Učestvujući u izgradnji fosfolipidnog dvosloja bioloških mambrana, on reguliše njihovu fluidnost, propustljivost i rigidnost, a samim tim i funkcionalna svojstva membranskih proteina, poput jonskih kanala i transmiterskih receptora. Metabolizam holesterola predstavlja važan aspekt sinaptičke plastičnosti, jer je pokazano da je holesterol neophodan za biogenezu i transport sinaptičkih vezikula, kao i za prvilnu funkcionalnu organizaciju lipidnih ostvaca. Od svih organa u telu, mozak sadrži najviše holesterola. Održavanje homeostaze holesterola neophodno je za normalno i neometano funkcionisanje CNS..., Ageing of the central nervous system is associated with a number of changes that disturb nerve function, especially motor control and cognitive abilities. It is believed that cognitive disorders in aging are consequence of reduced synaptic plasticity, especially in the cortex and hippocampus, brain regions extremely important for learning and memory processes. Dominant factor that can influence aging in general, and therefore the aging of the brain is reduced diet regime, without malnutrition. In addition to being known for decades that reduced caloric intake prolongs life span of many species, including mammals, it is shown that it delays and alleviates age-dependent changes.Cholesterol is the most abundant lipid in mammalian cells. By participating in the construction of phospholipid bilayer of biological membranes, it regulates their fluidity, permeability and rigidity, and consequently the functional properties of membrane proteins, such as ion channels and transmmitters receptors. Cholesterol metabolism represents one aspect of synaptic plasticity, as has been shown that cholesterol is essential for biogenesis of synaptic vesicles, and vesicle transport, as well as for proper functional organization of lipid rafts. The brain contains the most cholesterol of all the organs in the body. Maintenance of cholesterol homeostasis is essential for proper functioning of the central nervous system...",
publisher = "Belgrade: Faculty of Biology, University of Belgrade",
journal = "Faculty of Biology, University of Belgrade",
title = "Uticaj starenja i dugotrajne dijetalne restrikcije na metabolizam holesterola u prednjem mozgu pacova, Effects of aging and long-term dietary restrictions on cholesterol metabolism in the rat forebrain",
doi = "10.2298/BG20120709SMILJANIC",
pages = "1-128",
url = "https://hdl.handle.net/21.15107/rcub_nardus_2017"
}

Smiljanić, K.. (2012). Uticaj starenja i dugotrajne dijetalne restrikcije na metabolizam holesterola u prednjem mozgu pacova. in Faculty of Biology, University of Belgrade
Belgrade: Faculty of Biology, University of Belgrade., 1-128.
https://doi.org/10.2298/BG20120709SMILJANIC
https://hdl.handle.net/21.15107/rcub_nardus_2017

Smiljanić K. Uticaj starenja i dugotrajne dijetalne restrikcije na metabolizam holesterola u prednjem mozgu pacova. in Faculty of Biology, University of Belgrade. 2012;:1-128.
doi:10.2298/BG20120709SMILJANIC
https://hdl.handle.net/21.15107/rcub_nardus_2017 .

Smiljanić, Kosara, "Uticaj starenja i dugotrajne dijetalne restrikcije na metabolizam holesterola u prednjem mozgu pacova" in Faculty of Biology, University of Belgrade (2012):1-128,
https://doi.org/10.2298/BG20120709SMILJANIC .,
https://hdl.handle.net/21.15107/rcub_nardus_2017 .

TY  - JOUR
AU  - Smiljanić, Kosara
AU  - Lavrnja, Irena
AU  - Mladenović, Aleksandra
AU  - Ruždijić, Sabera
AU  - Stojiljković, Mirjana B
AU  - Peković, Sanja
AU  - Kanazir, Selma
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1357
AB  - Maintaining the cholesterol homeostasis is essential for normal CNS functioning. The enzyme responsible for elimination of cholesterol excess from the brain is cholesterol 24-hydroxylase (Cyp46). Since cholesterol homeostasis is disrupted following brain injury, in this study we examined the effect of right sensorimotor cortex suction ablation on cellular and temporal pattern of Cyp46 expression in the rat brain. Increased expression of Cyp46 at the lesion site at all post injury time points (2, 7, 14, 28 and 45 days post injury, dpi) was detected. Double immunofluorescence staining revealed colocalization of Cyp46 expression with different types of glial cells in time-dependent manner. In ED1(+) microglia/macrophages Cyp46 expression was most prominent at 2 and 7 dpi, whereas Cyp46 immunoreactivity persisted in reactive astrocytes throughout all time points post-injury. However, during the first 2 weeks Cyp46 expression was enhanced in both GFAP(+) and Vim(+) astrocytes, while at 28 and 45 dpi its expression was mostly associated with GFAP(+) cells. Pattern of neuronal Cyp46 expression remained unchanged after the lesion, i.e. Cyp46 immunostaining was detected in dendrites and cell body, but not in axons. The results of this study clearly demonstrate that in pathological conditions, like brain injury, Cyp46 displayed atypical expression, being expressed not only in neuronal cells, but also in microglia and astrocytes. Therefore, injury-induced expression of Cyp46 in microglial and astroglial cells may be involved in the post-injury removal of damaged cell membranes contributing to re-establishment of the brain cholesterol homeostasis.
T2  - Histochemistry and Cell Biology
T1  - Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner
IS  - 2
VL  - 134
EP  - 169
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1357
ER  - 

@article{
author = "Smiljanić, Kosara and Lavrnja, Irena and Mladenović, Aleksandra and Ruždijić, Sabera and Stojiljković, Mirjana B and Peković, Sanja and Kanazir, Selma",
year = "2010",
abstract = "Maintaining the cholesterol homeostasis is essential for normal CNS functioning. The enzyme responsible for elimination of cholesterol excess from the brain is cholesterol 24-hydroxylase (Cyp46). Since cholesterol homeostasis is disrupted following brain injury, in this study we examined the effect of right sensorimotor cortex suction ablation on cellular and temporal pattern of Cyp46 expression in the rat brain. Increased expression of Cyp46 at the lesion site at all post injury time points (2, 7, 14, 28 and 45 days post injury, dpi) was detected. Double immunofluorescence staining revealed colocalization of Cyp46 expression with different types of glial cells in time-dependent manner. In ED1(+) microglia/macrophages Cyp46 expression was most prominent at 2 and 7 dpi, whereas Cyp46 immunoreactivity persisted in reactive astrocytes throughout all time points post-injury. However, during the first 2 weeks Cyp46 expression was enhanced in both GFAP(+) and Vim(+) astrocytes, while at 28 and 45 dpi its expression was mostly associated with GFAP(+) cells. Pattern of neuronal Cyp46 expression remained unchanged after the lesion, i.e. Cyp46 immunostaining was detected in dendrites and cell body, but not in axons. The results of this study clearly demonstrate that in pathological conditions, like brain injury, Cyp46 displayed atypical expression, being expressed not only in neuronal cells, but also in microglia and astrocytes. Therefore, injury-induced expression of Cyp46 in microglial and astroglial cells may be involved in the post-injury removal of damaged cell membranes contributing to re-establishment of the brain cholesterol homeostasis.",
journal = "Histochemistry and Cell Biology",
title = "Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner",
number = "2",
volume = "134",
pages = "169",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1357"
}

Smiljanić, K., Lavrnja, I., Mladenović, A., Ruždijić, S., Stojiljković, M. B., Peković, S.,& Kanazir, S.. (2010). Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner. in Histochemistry and Cell Biology, 134(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1357

Smiljanić K, Lavrnja I, Mladenović A, Ruždijić S, Stojiljković MB, Peković S, Kanazir S. Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner. in Histochemistry and Cell Biology. 2010;134(2):null-169.
https://hdl.handle.net/21.15107/rcub_ibiss_1357 .

Smiljanić, Kosara, Lavrnja, Irena, Mladenović, Aleksandra, Ruždijić, Sabera, Stojiljković, Mirjana B, Peković, Sanja, Kanazir, Selma, "Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner" in Histochemistry and Cell Biology, 134, no. 2 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1357 .

TY  - JOUR
AU  - Perović, Milka
AU  - Mladenović, Aleksandra
AU  - Smiljanić, Kosara
AU  - Tanić, Nikola T
AU  - Rakić, Ljubisav
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1420
AB  - Expression profiles of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), apolipoprotein E (ApoE) and cholesterol 24S-hydroxylase (CYP46), proteins involved in cholesterol biosynthesis, transport and excretion from the CNS, were analyzed in the rat cortex, hippocampus and cerebellum as a function of aging (6-24 months) and in response to long-term dietary restriction (DR). Age-related increases for all three mRNAs were observed, with the highest induction found for Cyp46 in the cortex and hippocampus of 24-month-old animals. DR maintained stable levels of Cyp46, HMGR, and ApoE mRNAs during aging, exhibiting an attenuating effect on age-related changes through specific temporal and regional pattern. Neither age nor DR had any prominent effects at the protein level, except for Cyp46 and ApoE protein levels in the hippocampus and cerebellum, respectively. Overall, the changes in the cerebellum were different from those in the cortex and hippocampus. Our results demonstrated a modulatory effect of DR on age-related changes of CYP46, HMGR, and ApoE and suggest that the anti-aging effect of DR is in part mediated though transcriptional modulation of cholesterol metabolism genes in the rat brain.
T2  - Biogerontology
T1  - Expression of cholesterol homeostasis genes in the brain of the male rat is affected by age and dietary restriction
IS  - 6
VL  - 10
EP  - 745
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1420
ER  - 

@article{
author = "Perović, Milka and Mladenović, Aleksandra and Smiljanić, Kosara and Tanić, Nikola T and Rakić, Ljubisav and Ruždijić, Sabera and Kanazir, Selma",
year = "2009",
abstract = "Expression profiles of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), apolipoprotein E (ApoE) and cholesterol 24S-hydroxylase (CYP46), proteins involved in cholesterol biosynthesis, transport and excretion from the CNS, were analyzed in the rat cortex, hippocampus and cerebellum as a function of aging (6-24 months) and in response to long-term dietary restriction (DR). Age-related increases for all three mRNAs were observed, with the highest induction found for Cyp46 in the cortex and hippocampus of 24-month-old animals. DR maintained stable levels of Cyp46, HMGR, and ApoE mRNAs during aging, exhibiting an attenuating effect on age-related changes through specific temporal and regional pattern. Neither age nor DR had any prominent effects at the protein level, except for Cyp46 and ApoE protein levels in the hippocampus and cerebellum, respectively. Overall, the changes in the cerebellum were different from those in the cortex and hippocampus. Our results demonstrated a modulatory effect of DR on age-related changes of CYP46, HMGR, and ApoE and suggest that the anti-aging effect of DR is in part mediated though transcriptional modulation of cholesterol metabolism genes in the rat brain.",
journal = "Biogerontology",
title = "Expression of cholesterol homeostasis genes in the brain of the male rat is affected by age and dietary restriction",
number = "6",
volume = "10",
pages = "745",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1420"
}

Perović, M., Mladenović, A., Smiljanić, K., Tanić, N. T., Rakić, L., Ruždijić, S.,& Kanazir, S.. (2009). Expression of cholesterol homeostasis genes in the brain of the male rat is affected by age and dietary restriction. in Biogerontology, 10(6).
https://hdl.handle.net/21.15107/rcub_ibiss_1420

Perović M, Mladenović A, Smiljanić K, Tanić NT, Rakić L, Ruždijić S, Kanazir S. Expression of cholesterol homeostasis genes in the brain of the male rat is affected by age and dietary restriction. in Biogerontology. 2009;10(6):null-745.
https://hdl.handle.net/21.15107/rcub_ibiss_1420 .

Perović, Milka, Mladenović, Aleksandra, Smiljanić, Kosara, Tanić, Nikola T, Rakić, Ljubisav, Ruždijić, Sabera, Kanazir, Selma, "Expression of cholesterol homeostasis genes in the brain of the male rat is affected by age and dietary restriction" in Biogerontology, 10, no. 6 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1420 .