TY  - JOUR
AU  - Jović, Milena
AU  - Lončarević-Vasiljković, Nataša
AU  - Ivković, Sanja
AU  - Dinić, Jelena
AU  - Milanović, Desanka
AU  - Zloković, Berislav
AU  - Kanazir, Selma
PY  - 2019
UR  - http://dx.plos.org/10.1371/journal.pone.0216726
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6522015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3405
AB  - Dystrophic neurites and activated microglia are one of the main neuropathological characteristics of Alzheimer's disease (AD). Although the use of supplements with omega-3 fatty acids has been associated with reduced risk and lessened AD pathology, it still remains elusive whether such a treatment could affect dystrophic neurites (DNs) formation and microglia/macrophage behavior in the early phase of disease. We analyzed the effects of short-term (3 weeks) fish oil supplementation on DNs formation, tau hyperphosphorylation, Amyloid-beta peptide 1-42 (Aβ42) levels and microglial/macrophage response to AD pathology in the parietal cortex of 4-month-old 5xFAD mice, a mouse model of AD. The present study shows for the first time that short-term FO supplementation applied in presymptomatic stage of AD, alters the behaviour of microglia/macrophages prompting them to establish a physical barrier around amyloid plaques. This barrier significantly suppresses DNs formation through the reduction of both Aβ content and tau hyperphosphorylation. Moreover, the short-term FO treatment neither suppresses inflammation nor enhances phagocytic properties of microglia/macrophages in the response to Aβ pathology, the effects most commonly attributed to the fish oil supplementation. Our findings suggest that fish oil consumption may play an important role in modulating microglial/macrophage response and ameliorating the AD pathology in presymptomatic stage of Alzheimer's disease.
T2  - PloS One
T1  - Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.
IS  - 5
VL  - 14
DO  - 10.1371/journal.pone.0216726
SP  - e0216726
ER  - 

@article{
author = "Jović, Milena and Lončarević-Vasiljković, Nataša and Ivković, Sanja and Dinić, Jelena and Milanović, Desanka and Zloković, Berislav and Kanazir, Selma",
year = "2019",
abstract = "Dystrophic neurites and activated microglia are one of the main neuropathological characteristics of Alzheimer's disease (AD). Although the use of supplements with omega-3 fatty acids has been associated with reduced risk and lessened AD pathology, it still remains elusive whether such a treatment could affect dystrophic neurites (DNs) formation and microglia/macrophage behavior in the early phase of disease. We analyzed the effects of short-term (3 weeks) fish oil supplementation on DNs formation, tau hyperphosphorylation, Amyloid-beta peptide 1-42 (Aβ42) levels and microglial/macrophage response to AD pathology in the parietal cortex of 4-month-old 5xFAD mice, a mouse model of AD. The present study shows for the first time that short-term FO supplementation applied in presymptomatic stage of AD, alters the behaviour of microglia/macrophages prompting them to establish a physical barrier around amyloid plaques. This barrier significantly suppresses DNs formation through the reduction of both Aβ content and tau hyperphosphorylation. Moreover, the short-term FO treatment neither suppresses inflammation nor enhances phagocytic properties of microglia/macrophages in the response to Aβ pathology, the effects most commonly attributed to the fish oil supplementation. Our findings suggest that fish oil consumption may play an important role in modulating microglial/macrophage response and ameliorating the AD pathology in presymptomatic stage of Alzheimer's disease.",
journal = "PloS One",
title = "Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.",
number = "5",
volume = "14",
doi = "10.1371/journal.pone.0216726",
pages = "e0216726"
}

Jović, M., Lončarević-Vasiljković, N., Ivković, S., Dinić, J., Milanović, D., Zloković, B.,& Kanazir, S.. (2019). Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.. in PloS One, 14(5), e0216726.
https://doi.org/10.1371/journal.pone.0216726

Jović M, Lončarević-Vasiljković N, Ivković S, Dinić J, Milanović D, Zloković B, Kanazir S. Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.. in PloS One. 2019;14(5):e0216726.
doi:10.1371/journal.pone.0216726 .

Jović, Milena, Lončarević-Vasiljković, Nataša, Ivković, Sanja, Dinić, Jelena, Milanović, Desanka, Zloković, Berislav, Kanazir, Selma, "Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model." in PloS One, 14, no. 5 (2019):e0216726,
https://doi.org/10.1371/journal.pone.0216726 . .

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  - Milanović, Desanka
AU  - Petrovic, Snjezana
AU  - Brkić, Marjana
AU  - Avramović, Vladimir
AU  - Perović, Milka
AU  - Ivković, Sanja
AU  - Glibetić, Marija
AU  - Kanazir, Selma
PY  - 2018
UR  - http://www.mdpi.com/2072-6643/10/9/1250
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3136
AB  - Long-term fish oil (FO) supplementation is able to improve Alzheimer's disease (AD) pathology. We aimed to determine the impact of short-term fish oil (FO) intake on phospholipids composition and plaque pathology in 5xFAD mice, a widely used animal model of AD. A 3-week-long FO supplementation administered at 3 months of age decreased the number of dense core plaques in the 5xFAD cortex and changed phospholipids in the livers and brains of wild-type (Wt) and 5xFAD mice. Livers of both genotypes responded by increase of n-3 and reciprocal decrease of n-6 fatty acids. In Wt brains, FO supplementation induced elevation of n-3 fatty acids and subsequent enhancement of n-6/n-3 ratio. However, in 5xFAD brains the improved n-6/n-3 ratio was mainly due to FO-induced decrease in arachidonic and adrenic n-6 fatty acids. Also, brain and liver abundance of n-3 fatty acids were strongly correlated in Wts, oppositely to 5xFADs where significant brain-liver correlation exists only for n-6 fatty acids. Expression of omega-3 transporter Mfs2a remained unchanged after FO supplementation. We have demonstrated that even a short-term FO intake improves the phospholipid composition and has a significant effect on plaque burden in 5xFAD brains when applied in early stages of AD pathology.
T2  - Nutrients
T1  - Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease.
IS  - 9
VL  - 10
DO  - 10.3390/nu10091250
SP  - 1250
ER  - 

@article{
author = "Milanović, Desanka and Petrovic, Snjezana and Brkić, Marjana and Avramović, Vladimir and Perović, Milka and Ivković, Sanja and Glibetić, Marija and Kanazir, Selma",
year = "2018",
abstract = "Long-term fish oil (FO) supplementation is able to improve Alzheimer's disease (AD) pathology. We aimed to determine the impact of short-term fish oil (FO) intake on phospholipids composition and plaque pathology in 5xFAD mice, a widely used animal model of AD. A 3-week-long FO supplementation administered at 3 months of age decreased the number of dense core plaques in the 5xFAD cortex and changed phospholipids in the livers and brains of wild-type (Wt) and 5xFAD mice. Livers of both genotypes responded by increase of n-3 and reciprocal decrease of n-6 fatty acids. In Wt brains, FO supplementation induced elevation of n-3 fatty acids and subsequent enhancement of n-6/n-3 ratio. However, in 5xFAD brains the improved n-6/n-3 ratio was mainly due to FO-induced decrease in arachidonic and adrenic n-6 fatty acids. Also, brain and liver abundance of n-3 fatty acids were strongly correlated in Wts, oppositely to 5xFADs where significant brain-liver correlation exists only for n-6 fatty acids. Expression of omega-3 transporter Mfs2a remained unchanged after FO supplementation. We have demonstrated that even a short-term FO intake improves the phospholipid composition and has a significant effect on plaque burden in 5xFAD brains when applied in early stages of AD pathology.",
journal = "Nutrients",
title = "Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease.",
number = "9",
volume = "10",
doi = "10.3390/nu10091250",
pages = "1250"
}

Milanović, D., Petrovic, S., Brkić, M., Avramović, V., Perović, M., Ivković, S., Glibetić, M.,& Kanazir, S.. (2018). Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease.. in Nutrients, 10(9), 1250.
https://doi.org/10.3390/nu10091250

Milanović D, Petrovic S, Brkić M, Avramović V, Perović M, Ivković S, Glibetić M, Kanazir S. Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease.. in Nutrients. 2018;10(9):1250.
doi:10.3390/nu10091250 .

Milanović, Desanka, Petrovic, Snjezana, Brkić, Marjana, Avramović, Vladimir, Perović, Milka, Ivković, Sanja, Glibetić, Marija, Kanazir, Selma, "Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease." in Nutrients, 10, no. 9 (2018):1250,
https://doi.org/10.3390/nu10091250 . .

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 . .