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  - Mladenović, Aleksandra
AU  - Perović, Milka
AU  - Tesić, Vesna T
AU  - Tanić, Nikola T
AU  - Rakić, Ljubisav
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1414
AB  - Brain aging is related to the numerous structural and functional changes including decreased synaptic plasticity. The beneficial effects of dietary restriction (DR) are well known but insufficiently investigated at the level of plasticity-related markers. Therefore, the aim of this study was to examine the expression profiles of proteins structurally and functionally related to synapses-growth-associated protein 43 (GAP-43), synaptophysin (SPH) and alpha-synuclein (alpha-Syn), in the course of aging and in response to long-term DR. The mRNA and protein levels of three presynaptic proteins were assessed by Real Time RT-PCR and Western blotting in the cortex and hippocampus of young (6-month-old), middle-aged (12-month-old), aged (18-month-old) and old (24-month-old) male Wistar rats fed ad libitum and exposed to DR starting from 6 months of age. We observed that long-term DR modulated age-related transcriptional changes by maintaining stable mRNAs levels in the cortex. No major age-related changes of the protein levels were observed in the cortex, while the specific temporal decline was detected in the hippocampus for all three proteins. The SPH levels were decreased across lifespan (0.8-, 0.8- and 0.6-fold change at 12,18 and 24 months), while the significant decrease of GAP-43 and alpha-Syn protein was detected at 24 months of age (0.6- and 0.7-fold decrease, respectively). Long-term DR eliminated this decline by increasing GAP-43, SPH and alpha-Syn protein levels (1.7-, 1.7- and 1.6-fold, respectively) thus reverting protein levels to the values measured in 6-month-old animals. Specific pattern of changes observed in the hippocampus identifies this structure as more vulnerable to the processes of aging and with a more pronounced response to the DR effects. The observed DR-induced stabilization of the levels of three presynaptic proteins indicates the beneficial effect of DR on age-related decline in the capacity for synaptic plasticity. (C) 2009 Elsevier Ltd. All rights reserved.
T2  - Neurochemistry International
T1  - Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat
IS  - 2
VL  - 56
EP  - 255
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1414
ER  - 

@article{
author = "Mladenović, Aleksandra and Perović, Milka and Tesić, Vesna T and Tanić, Nikola T and Rakić, Ljubisav and Ruždijić, Sabera and Kanazir, Selma",
year = "2010",
abstract = "Brain aging is related to the numerous structural and functional changes including decreased synaptic plasticity. The beneficial effects of dietary restriction (DR) are well known but insufficiently investigated at the level of plasticity-related markers. Therefore, the aim of this study was to examine the expression profiles of proteins structurally and functionally related to synapses-growth-associated protein 43 (GAP-43), synaptophysin (SPH) and alpha-synuclein (alpha-Syn), in the course of aging and in response to long-term DR. The mRNA and protein levels of three presynaptic proteins were assessed by Real Time RT-PCR and Western blotting in the cortex and hippocampus of young (6-month-old), middle-aged (12-month-old), aged (18-month-old) and old (24-month-old) male Wistar rats fed ad libitum and exposed to DR starting from 6 months of age. We observed that long-term DR modulated age-related transcriptional changes by maintaining stable mRNAs levels in the cortex. No major age-related changes of the protein levels were observed in the cortex, while the specific temporal decline was detected in the hippocampus for all three proteins. The SPH levels were decreased across lifespan (0.8-, 0.8- and 0.6-fold change at 12,18 and 24 months), while the significant decrease of GAP-43 and alpha-Syn protein was detected at 24 months of age (0.6- and 0.7-fold decrease, respectively). Long-term DR eliminated this decline by increasing GAP-43, SPH and alpha-Syn protein levels (1.7-, 1.7- and 1.6-fold, respectively) thus reverting protein levels to the values measured in 6-month-old animals. Specific pattern of changes observed in the hippocampus identifies this structure as more vulnerable to the processes of aging and with a more pronounced response to the DR effects. The observed DR-induced stabilization of the levels of three presynaptic proteins indicates the beneficial effect of DR on age-related decline in the capacity for synaptic plasticity. (C) 2009 Elsevier Ltd. All rights reserved.",
journal = "Neurochemistry International",
title = "Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat",
number = "2",
volume = "56",
pages = "255",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1414"
}

Mladenović, A., Perović, M., Tesić, V. T., Tanić, N. T., Rakić, L., Ruždijić, S.,& Kanazir, S.. (2010). Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat. in Neurochemistry International, 56(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1414

Mladenović A, Perović M, Tesić VT, Tanić NT, Rakić L, Ruždijić S, Kanazir S. Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat. in Neurochemistry International. 2010;56(2):null-255.
https://hdl.handle.net/21.15107/rcub_ibiss_1414 .

Mladenović, Aleksandra, Perović, Milka, Tesić, Vesna T, Tanić, Nikola T, Rakić, Ljubisav, Ruždijić, Sabera, Kanazir, Selma, "Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat" in Neurochemistry International, 56, no. 2 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1414 .