TY  - JOUR
AU  - Jovanović Macura, Irena
AU  - Đuričić, Ivana
AU  - Major, Tamara
AU  - Milanović, Desanka
AU  - Šobajić, Slađana
AU  - Kanazir, Selma
AU  - Ivković, Sanja
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12541
AB  - Introduction: During fetal development, the proper development of neural and visual systems relies on the maternal supplementation of omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources of omega-3, such as fish oil (FO). This supplementation has been linked to a reduced risk of preterm birth, pre-eclampsia, and perinatal depression. Recently, higher doses of omega-3 supplementation have been recommended for pregnant women. Considering that omega-3 fatty acids, particularly docosahexaenoic acid (DHA), play a crucial role in maintaining the delicate homeostasis required for the proper functioning of the retina and photoreceptors the effects of high-dose fish oil (FO) supplementation during pregnancy and lactation on the retina and retinal pigmented epithelium (RPE) in healthy offspring warrant better understanding.  Methods: The fatty acid content and the changes in the expression of the genes regulating cholesterol homeostasis and DHA transport in the retina and RPE were evaluated following the high-dose FO supplementation.  Results: Our study demonstrated that despite the high-dose FO treatment during pregnancy and lactation, the rigorous DHA homeostasis in the retina and RPE of the two-month-old offspring remained balanced. Another significant finding of this study is the increase in the expression levels of major facilitator superfamily domain-containing protein (Mfsd2a), a primary DHA transporter. Mfsd2a also serves as a major regulator of transcytosis during development, and a reduction in Mfsd2a levels poses a major risk for the development of leaky blood vessels.  Conclusion: Impairment of the blood-retinal barrier (BRB) is associated with the development of numerous ocular diseases, and a better understanding of how to manipulate transcytosis in the BRB during development can enhance drug delivery through the BRB or contribute to the repair of central nervous system (CNS) barriers.
T2  - Frontiers in Nutrition
T1  - The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring
VL  - 10
SP  - 1330414
DO  - 10.3389/fnut.2023.1330414
ER  - 

@article{
author = "Jovanović Macura, Irena and Đuričić, Ivana and Major, Tamara and Milanović, Desanka and Šobajić, Slađana and Kanazir, Selma and Ivković, Sanja",
year = "2024",
abstract = "Introduction: During fetal development, the proper development of neural and visual systems relies on the maternal supplementation of omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources of omega-3, such as fish oil (FO). This supplementation has been linked to a reduced risk of preterm birth, pre-eclampsia, and perinatal depression. Recently, higher doses of omega-3 supplementation have been recommended for pregnant women. Considering that omega-3 fatty acids, particularly docosahexaenoic acid (DHA), play a crucial role in maintaining the delicate homeostasis required for the proper functioning of the retina and photoreceptors the effects of high-dose fish oil (FO) supplementation during pregnancy and lactation on the retina and retinal pigmented epithelium (RPE) in healthy offspring warrant better understanding.  Methods: The fatty acid content and the changes in the expression of the genes regulating cholesterol homeostasis and DHA transport in the retina and RPE were evaluated following the high-dose FO supplementation.  Results: Our study demonstrated that despite the high-dose FO treatment during pregnancy and lactation, the rigorous DHA homeostasis in the retina and RPE of the two-month-old offspring remained balanced. Another significant finding of this study is the increase in the expression levels of major facilitator superfamily domain-containing protein (Mfsd2a), a primary DHA transporter. Mfsd2a also serves as a major regulator of transcytosis during development, and a reduction in Mfsd2a levels poses a major risk for the development of leaky blood vessels.  Conclusion: Impairment of the blood-retinal barrier (BRB) is associated with the development of numerous ocular diseases, and a better understanding of how to manipulate transcytosis in the BRB during development can enhance drug delivery through the BRB or contribute to the repair of central nervous system (CNS) barriers.",
journal = "Frontiers in Nutrition",
title = "The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring",
volume = "10",
pages = "1330414",
doi = "10.3389/fnut.2023.1330414"
}

Jovanović Macura, I., Đuričić, I., Major, T., Milanović, D., Šobajić, S., Kanazir, S.,& Ivković, S.. (2024). The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring. in Frontiers in Nutrition, 10, 1330414.
https://doi.org/10.3389/fnut.2023.1330414

Jovanović Macura I, Đuričić I, Major T, Milanović D, Šobajić S, Kanazir S, Ivković S. The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring. in Frontiers in Nutrition. 2024;10:1330414.
doi:10.3389/fnut.2023.1330414 .

Jovanović Macura, Irena, Đuričić, Ivana, Major, Tamara, Milanović, Desanka, Šobajić, Slađana, Kanazir, Selma, Ivković, Sanja, "The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring" in Frontiers in Nutrition, 10 (2024):1330414,
https://doi.org/10.3389/fnut.2023.1330414 . .

TY  - CONF
AU  - Jovanović Macura, Irena
AU  - Đuričić, Ivana
AU  - Major, Tamara
AU  - Milanović, Desanka
AU  - Brkić, Marjana
AU  - Šobajić, Slađana
AU  - Kanazir, Selma
AU  - Ivković, Sanja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11049
AB  - Mfsd2a is expressed mainly in the endothelial cells and is an essential regulator of blood vessel transcytosis. Therefore, decrease in Mfsd2a expression can be a risk factor for developing leaky blood vessels. Mfsd2a is also the main docosahexaenoic acid (DHA, C22:6n3) transporter. DHA, an omega-3 fatty acid, is one of the main structural lipids of the neuronal and vascular retina, crucial for the normal functioning of photoreceptors (PRs). However, the capacity of the retina to synthesize DHA is limited, and the maintenance of retinal DHA content relies on the uptake from bloodborne lipids. The currently recommended FO doses yielded low PUFAs tissue bioavailability, and supplementation with higher doses has been increasingly recommended. Nevertheless, the effects of higher FO doses on retinal Mfsd2a expression and blood vessels coverage are unknown. Western blot and qPCR analyses showed that high dose FO supplementation increased Mfsd2a expression in the retina. Immunohistochemical analyses of Mfsd2a expression on retinal blood vessels (labeled with 488-conjugated Lycopersicon esculentum, lectin) and subsequent ImageJ analyses revealed 1.32-fold increase in the Mfsd2a retinal blood vessel coverage. In the same time the pericyte blood vessel coverage (CD13+ cells) was not affected with FO supplementation, and the increase in Mfsd2a blood vessel expression is not the result of the increased pericyte coverage. Therefore, the high-dose FO supplementation emerges as the prophylactic fortifier of the retinal blood vessels that can serve either as prophylaxis in the healthy eye or as an adjuvant in developing targeted manipulations of the barrier during diseases.
PB  - Belgrade : Serbian Neurocardiological Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - The high-dose fish oil (FO) supplementation increased Mfsd2a expression in the retina of healthy mice
SP  - 66
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11049
ER  - 

@conference{
author = "Jovanović Macura, Irena and Đuričić, Ivana and Major, Tamara and Milanović, Desanka and Brkić, Marjana and Šobajić, Slađana and Kanazir, Selma and Ivković, Sanja",
year = "2023",
abstract = "Mfsd2a is expressed mainly in the endothelial cells and is an essential regulator of blood vessel transcytosis. Therefore, decrease in Mfsd2a expression can be a risk factor for developing leaky blood vessels. Mfsd2a is also the main docosahexaenoic acid (DHA, C22:6n3) transporter. DHA, an omega-3 fatty acid, is one of the main structural lipids of the neuronal and vascular retina, crucial for the normal functioning of photoreceptors (PRs). However, the capacity of the retina to synthesize DHA is limited, and the maintenance of retinal DHA content relies on the uptake from bloodborne lipids. The currently recommended FO doses yielded low PUFAs tissue bioavailability, and supplementation with higher doses has been increasingly recommended. Nevertheless, the effects of higher FO doses on retinal Mfsd2a expression and blood vessels coverage are unknown. Western blot and qPCR analyses showed that high dose FO supplementation increased Mfsd2a expression in the retina. Immunohistochemical analyses of Mfsd2a expression on retinal blood vessels (labeled with 488-conjugated Lycopersicon esculentum, lectin) and subsequent ImageJ analyses revealed 1.32-fold increase in the Mfsd2a retinal blood vessel coverage. In the same time the pericyte blood vessel coverage (CD13+ cells) was not affected with FO supplementation, and the increase in Mfsd2a blood vessel expression is not the result of the increased pericyte coverage. Therefore, the high-dose FO supplementation emerges as the prophylactic fortifier of the retinal blood vessels that can serve either as prophylaxis in the healthy eye or as an adjuvant in developing targeted manipulations of the barrier during diseases.",
publisher = "Belgrade : Serbian Neurocardiological Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "The high-dose fish oil (FO) supplementation increased Mfsd2a expression in the retina of healthy mice",
pages = "66",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11049"
}

Jovanović Macura, I., Đuričić, I., Major, T., Milanović, D., Brkić, M., Šobajić, S., Kanazir, S.,& Ivković, S.. (2023). The high-dose fish oil (FO) supplementation increased Mfsd2a expression in the retina of healthy mice. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neurocardiological Society., 66.
https://hdl.handle.net/21.15107/rcub_vinar_11049

Jovanović Macura I, Đuričić I, Major T, Milanović D, Brkić M, Šobajić S, Kanazir S, Ivković S. The high-dose fish oil (FO) supplementation increased Mfsd2a expression in the retina of healthy mice. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:66.
https://hdl.handle.net/21.15107/rcub_vinar_11049 .

Jovanović Macura, Irena, Đuričić, Ivana, Major, Tamara, Milanović, Desanka, Brkić, Marjana, Šobajić, Slađana, Kanazir, Selma, Ivković, Sanja, "The high-dose fish oil (FO) supplementation increased Mfsd2a expression in the retina of healthy mice" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):66,
https://hdl.handle.net/21.15107/rcub_vinar_11049 .

TY  - JOUR
AU  - Jovanović Macura, Irena
AU  - Živanović, Ana
AU  - Perović, Milka
AU  - Ćirić, Jelena
AU  - Major, Tamara
AU  - Kanazir, Selma
AU  - Ivković, Sanja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11643
AB  - Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer’s disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging. We analyzed the changes in the mRNA and protein expression of major facilitator superfamily domain-containing protein2a (Mfsd2a), the major regulator of transcytosis, and of Aquaporin4 (Aqp4), the key player implicated in the functioning of the glymphatic system, in the retinas of 4- and 12-month-old WT and 5xFAD female mice. A strong decrease in the Mfsd2a mRNA and protein expression was observed in the 4 M and 12 M 5xFAD and 12 M WT retinas. The increase in the expression of srebp1-c could be at least partially responsible for the Mfsd2a decrease in the 4 M 5xFAD retinas. The decrease in the pericyte (CD13+) coverage of retinal blood vessels in the 4 M and 12 M 5xFAD retinas and in the 12 M WT retinas suggests that pericyte loss could be associated with the Mfsd2a downregulation in these experimental groups. The observed increase in Aqp4 expression in 4 M and 12 M 5xFAD and 12 M WT retinas accompanied by the decreased perivascular Aqp4 expression is indicative of the impaired glymphatic system. The findings in this study reveal the impaired Mfsd2a and Aqp4 expression and Aqp4 perivascular mislocalization in retinal blood vessels during physiological (WT) and pathological (5xFAD) aging, indicating their importance as putative targets for the development of new treatments that can improve the regulation of transcytosis or the function of the glymphatic system.
T2  - International Journal of Molecular Sciences
T1  - The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease
VL  - 24
IS  - 18
SP  - 14092
DO  - 10.3390/ijms241814092
ER  - 

@article{
author = "Jovanović Macura, Irena and Živanović, Ana and Perović, Milka and Ćirić, Jelena and Major, Tamara and Kanazir, Selma and Ivković, Sanja",
year = "2023",
abstract = "Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer’s disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging. We analyzed the changes in the mRNA and protein expression of major facilitator superfamily domain-containing protein2a (Mfsd2a), the major regulator of transcytosis, and of Aquaporin4 (Aqp4), the key player implicated in the functioning of the glymphatic system, in the retinas of 4- and 12-month-old WT and 5xFAD female mice. A strong decrease in the Mfsd2a mRNA and protein expression was observed in the 4 M and 12 M 5xFAD and 12 M WT retinas. The increase in the expression of srebp1-c could be at least partially responsible for the Mfsd2a decrease in the 4 M 5xFAD retinas. The decrease in the pericyte (CD13+) coverage of retinal blood vessels in the 4 M and 12 M 5xFAD retinas and in the 12 M WT retinas suggests that pericyte loss could be associated with the Mfsd2a downregulation in these experimental groups. The observed increase in Aqp4 expression in 4 M and 12 M 5xFAD and 12 M WT retinas accompanied by the decreased perivascular Aqp4 expression is indicative of the impaired glymphatic system. The findings in this study reveal the impaired Mfsd2a and Aqp4 expression and Aqp4 perivascular mislocalization in retinal blood vessels during physiological (WT) and pathological (5xFAD) aging, indicating their importance as putative targets for the development of new treatments that can improve the regulation of transcytosis or the function of the glymphatic system.",
journal = "International Journal of Molecular Sciences",
title = "The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease",
volume = "24",
number = "18",
pages = "14092",
doi = "10.3390/ijms241814092"
}

Jovanović Macura, I., Živanović, A., Perović, M., Ćirić, J., Major, T., Kanazir, S.,& Ivković, S.. (2023). The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease. in International Journal of Molecular Sciences, 24(18), 14092.
https://doi.org/10.3390/ijms241814092

Jovanović Macura I, Živanović A, Perović M, Ćirić J, Major T, Kanazir S, Ivković S. The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease. in International Journal of Molecular Sciences. 2023;24(18):14092.
doi:10.3390/ijms241814092 .

Jovanović Macura, Irena, Živanović, Ana, Perović, Milka, Ćirić, Jelena, Major, Tamara, Kanazir, Selma, Ivković, Sanja, "The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease" in International Journal of Molecular Sciences, 24, no. 18 (2023):14092,
https://doi.org/10.3390/ijms241814092 . .

TY  - JOUR
AU  - Perović, Milka
AU  - Ćirić, Jelena
AU  - Matović, Valentina
AU  - Srbovan, Maja
AU  - Koruga, Đuro
AU  - Kanazir, Selma
AU  - Ivković, Sanja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10854
AB  - Introduction In the present study, we assessed the effects of the hyper-harmonized-hydroxylated fullerene–water complex (3HFWC) on Alzheimer's disease (AD) neuropathological hallmarks in 5XFAD mice, an AD animal model. Methods The 3-week-old 5XFAD mice were exposed to 3HFWC water solution ad libitum for 3 months in the presymptomatic phase of pathology. The functional effects of the treatment were confirmed through near-infrared spectroscopy (NIRS) analysis through machine learning (ML) using artificial neural networks (ANNs) to classify the control and 3HFWC-treated brain tissue samples. The effects of 3HFWC treatment on amyloid-β (Aβ) accumulation, plaque formation, gliosis, and synaptic plasticity in cortical and hippocampal tissue were assessed. Results The 3HFWC treatment significantly decreased the amyloid-β plaque load in specific parts of the cerebral cortex. At the same time, 3HFWC treatment did not induce the activation of glia (astrocytes and microglia) nor did it negatively affect synaptic protein markers (GAP-43, synaptophysin, and PSD-95). Conclusion The obtained results point to the potential of 3HFWC, when applied in the presymptomatic phase of AD, to interfere with amyloid plaque formation without inducing AD-related pathological processes such as neuroinflammation, gliosis, and synaptic vulnerability.
T2  - CNS Neuroscience & Therapeutics
T1  - The presymptomatic treatment with 3HFWC nanosubstance decreased plaque load in 5XFAD mouse model of Alzheimer's disease
IS  - InPress
DO  - 10.1111/cns.14188
ER  - 

@article{
author = "Perović, Milka and Ćirić, Jelena and Matović, Valentina and Srbovan, Maja and Koruga, Đuro and Kanazir, Selma and Ivković, Sanja",
year = "2023",
abstract = "Introduction In the present study, we assessed the effects of the hyper-harmonized-hydroxylated fullerene–water complex (3HFWC) on Alzheimer's disease (AD) neuropathological hallmarks in 5XFAD mice, an AD animal model. Methods The 3-week-old 5XFAD mice were exposed to 3HFWC water solution ad libitum for 3 months in the presymptomatic phase of pathology. The functional effects of the treatment were confirmed through near-infrared spectroscopy (NIRS) analysis through machine learning (ML) using artificial neural networks (ANNs) to classify the control and 3HFWC-treated brain tissue samples. The effects of 3HFWC treatment on amyloid-β (Aβ) accumulation, plaque formation, gliosis, and synaptic plasticity in cortical and hippocampal tissue were assessed. Results The 3HFWC treatment significantly decreased the amyloid-β plaque load in specific parts of the cerebral cortex. At the same time, 3HFWC treatment did not induce the activation of glia (astrocytes and microglia) nor did it negatively affect synaptic protein markers (GAP-43, synaptophysin, and PSD-95). Conclusion The obtained results point to the potential of 3HFWC, when applied in the presymptomatic phase of AD, to interfere with amyloid plaque formation without inducing AD-related pathological processes such as neuroinflammation, gliosis, and synaptic vulnerability.",
journal = "CNS Neuroscience & Therapeutics",
title = "The presymptomatic treatment with 3HFWC nanosubstance decreased plaque load in 5XFAD mouse model of Alzheimer's disease",
number = "InPress",
doi = "10.1111/cns.14188"
}

Perović, M., Ćirić, J., Matović, V., Srbovan, M., Koruga, Đ., Kanazir, S.,& Ivković, S.. (2023). The presymptomatic treatment with 3HFWC nanosubstance decreased plaque load in 5XFAD mouse model of Alzheimer's disease. in CNS Neuroscience & Therapeutics(InPress).
https://doi.org/10.1111/cns.14188

Perović M, Ćirić J, Matović V, Srbovan M, Koruga Đ, Kanazir S, Ivković S. The presymptomatic treatment with 3HFWC nanosubstance decreased plaque load in 5XFAD mouse model of Alzheimer's disease. in CNS Neuroscience & Therapeutics. 2023;(InPress).
doi:10.1111/cns.14188 .

Perović, Milka, Ćirić, Jelena, Matović, Valentina, Srbovan, Maja, Koruga, Đuro, Kanazir, Selma, Ivković, Sanja, "The presymptomatic treatment with 3HFWC nanosubstance decreased plaque load in 5XFAD mouse model of Alzheimer's disease" in CNS Neuroscience & Therapeutics, no. InPress (2023),
https://doi.org/10.1111/cns.14188 . .

TY  - JOUR
AU  - Ćirić, Jelena
AU  - Tešić, Vesna
AU  - Milovanović, Nikola
AU  - Jovanović Macura, Irena
AU  - Ivković, Sanja
AU  - Kanazir, Selma
AU  - Perović, Milka
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10484
AB  - Glucocorticoids are the most potent anti-inflammatory agents known. Limited in vivo data are available to characterize the mechanism underlying their cognitive side effects and transient occurrence of steroid psychosis. Cholesterol is important for proper neurotransmission and brain plasticity, and disruption of its homeostasis in the brain has been closely associated with memory decline during aging and in age-related neurodegenerative disorders. In the present study, we assessed the direct effects of dexamethasone, a potent synthetic glucocorticoid, on the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24S-hydroxylase (CYP46A1), major enzymes involved in cholesterol synthesis, metabolism, and excretion, respectively. The effects of the dexamethasone were examined during aging, in the cortex and hippocampus of 6-, 12- and 18-month-old rats, and following long-term food restriction (FR). The most prominent change observed was the age-related decrease in ApoE mRNA regardless of the food regimen applied. In animals kept on FR, this decrease was accompanied by an increase in the mRNA expression of HMGCR and CYP46A1. The present study also demonstrates that food restriction reversed most of the dexamethasone-induced changes in the expression of genes involved in regulation of cholesterol homeostasis in aging rats, in a region-specific manner.
T2  - Brain Sciences
T1  - Food Restriction Counteracts Dexamethasone-Induced Downregulation of Genes Involved in Cholesterol Homeostasis in Rat Brain during Aging
VL  - 12
IS  - 10
SP  - 1297
DO  - 10.3390/brainsci12101297
ER  - 

@article{
author = "Ćirić, Jelena and Tešić, Vesna and Milovanović, Nikola and Jovanović Macura, Irena and Ivković, Sanja and Kanazir, Selma and Perović, Milka",
year = "2022",
abstract = "Glucocorticoids are the most potent anti-inflammatory agents known. Limited in vivo data are available to characterize the mechanism underlying their cognitive side effects and transient occurrence of steroid psychosis. Cholesterol is important for proper neurotransmission and brain plasticity, and disruption of its homeostasis in the brain has been closely associated with memory decline during aging and in age-related neurodegenerative disorders. In the present study, we assessed the direct effects of dexamethasone, a potent synthetic glucocorticoid, on the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24S-hydroxylase (CYP46A1), major enzymes involved in cholesterol synthesis, metabolism, and excretion, respectively. The effects of the dexamethasone were examined during aging, in the cortex and hippocampus of 6-, 12- and 18-month-old rats, and following long-term food restriction (FR). The most prominent change observed was the age-related decrease in ApoE mRNA regardless of the food regimen applied. In animals kept on FR, this decrease was accompanied by an increase in the mRNA expression of HMGCR and CYP46A1. The present study also demonstrates that food restriction reversed most of the dexamethasone-induced changes in the expression of genes involved in regulation of cholesterol homeostasis in aging rats, in a region-specific manner.",
journal = "Brain Sciences",
title = "Food Restriction Counteracts Dexamethasone-Induced Downregulation of Genes Involved in Cholesterol Homeostasis in Rat Brain during Aging",
volume = "12",
number = "10",
pages = "1297",
doi = "10.3390/brainsci12101297"
}

Ćirić, J., Tešić, V., Milovanović, N., Jovanović Macura, I., Ivković, S., Kanazir, S.,& Perović, M.. (2022). Food Restriction Counteracts Dexamethasone-Induced Downregulation of Genes Involved in Cholesterol Homeostasis in Rat Brain during Aging. in Brain Sciences, 12(10), 1297.
https://doi.org/10.3390/brainsci12101297

Ćirić J, Tešić V, Milovanović N, Jovanović Macura I, Ivković S, Kanazir S, Perović M. Food Restriction Counteracts Dexamethasone-Induced Downregulation of Genes Involved in Cholesterol Homeostasis in Rat Brain during Aging. in Brain Sciences. 2022;12(10):1297.
doi:10.3390/brainsci12101297 .

Ćirić, Jelena, Tešić, Vesna, Milovanović, Nikola, Jovanović Macura, Irena, Ivković, Sanja, Kanazir, Selma, Perović, Milka, "Food Restriction Counteracts Dexamethasone-Induced Downregulation of Genes Involved in Cholesterol Homeostasis in Rat Brain during Aging" in Brain Sciences, 12, no. 10 (2022):1297,
https://doi.org/10.3390/brainsci12101297 . .

TY  - JOUR
AU  - Jovanović Macura, Irena
AU  - Đuričić, Ivana
AU  - Major, Tamara
AU  - Milanović, Desanka
AU  - Brkić, Marjana
AU  - Šobajić, Slađana
AU  - Kanazir, Selma
AU  - Ivković, Sanja
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10478
AB  - The recommended fish oil (FO) supplementation doses often yield low omega-3 polyunsaturated fatty acids (PUFAs) tissue bioavailability, and higher doses (up to 10 g per day) have been increasingly recommended. However, the exact effects of such FO supplementation on the healthy retina and retinal pigmented epithelium (RPE) are unknown. Our study showed that the high dose FO treatment did not imbalance the rigorous docosahexaenoic acid (DHA, C22:6n3) homeostasis in the retina and RPE in the three-month-old female B6/SLJ mice. Instead, we have found the significant increase in the expression of Mfsd2a, the main DHA transporter. Mfsd2a is also an essential regulator of blood vessel transcytosis and the decrease in Mfsd2a expression can be a risk factor for developing leaky blood vessels. Therefore, the high-dose FO supplementation emerges as the prophylactic fortifier of the retinal blood vessels.
T2  - Journal of Functional Foods
T1  - The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice
VL  - 99
SP  - 105302
DO  - 10.1016/j.jff.2022.105302
ER  - 

@article{
author = "Jovanović Macura, Irena and Đuričić, Ivana and Major, Tamara and Milanović, Desanka and Brkić, Marjana and Šobajić, Slađana and Kanazir, Selma and Ivković, Sanja",
year = "2022",
abstract = "The recommended fish oil (FO) supplementation doses often yield low omega-3 polyunsaturated fatty acids (PUFAs) tissue bioavailability, and higher doses (up to 10 g per day) have been increasingly recommended. However, the exact effects of such FO supplementation on the healthy retina and retinal pigmented epithelium (RPE) are unknown. Our study showed that the high dose FO treatment did not imbalance the rigorous docosahexaenoic acid (DHA, C22:6n3) homeostasis in the retina and RPE in the three-month-old female B6/SLJ mice. Instead, we have found the significant increase in the expression of Mfsd2a, the main DHA transporter. Mfsd2a is also an essential regulator of blood vessel transcytosis and the decrease in Mfsd2a expression can be a risk factor for developing leaky blood vessels. Therefore, the high-dose FO supplementation emerges as the prophylactic fortifier of the retinal blood vessels.",
journal = "Journal of Functional Foods",
title = "The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice",
volume = "99",
pages = "105302",
doi = "10.1016/j.jff.2022.105302"
}

Jovanović Macura, I., Đuričić, I., Major, T., Milanović, D., Brkić, M., Šobajić, S., Kanazir, S.,& Ivković, S.. (2022). The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice. in Journal of Functional Foods, 99, 105302.
https://doi.org/10.1016/j.jff.2022.105302

Jovanović Macura I, Đuričić I, Major T, Milanović D, Brkić M, Šobajić S, Kanazir S, Ivković S. The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice. in Journal of Functional Foods. 2022;99:105302.
doi:10.1016/j.jff.2022.105302 .

Jovanović Macura, Irena, Đuričić, Ivana, Major, Tamara, Milanović, Desanka, Brkić, Marjana, Šobajić, Slađana, Kanazir, Selma, Ivković, Sanja, "The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice" in Journal of Functional Foods, 99 (2022):105302,
https://doi.org/10.1016/j.jff.2022.105302 . .

TY  - JOUR
AU  - Vujčić, Miroslava T.
AU  - Terzić, N
AU  - Ristić-Fira, Aleksandra
AU  - Kanazir, Selma
AU  - Ruždijić, Sabera
PY  - 2005
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2906
AB  - In order to contribute to the understanding of mechanisms by which regulatory proteins recognize genetic information stored in DNA, analyses of their interaction with specific nucleotides are usually performed. In this study, the electrophoretic mobility shift assay (EMSA) was applied to analyze the interaction of nuclear proteins from the liver of rats of different age i.e., young (3-month-old), middle-aged (12-month-old) and aged (24-month-old), with radioactively labelled synthetic oligonucleotide analogues, corresponding to GRE. The levels of GRE binding activity were assessed by quantitative densitometric scanning of the autoradiograms. The results showed statistically significant decreasing values of up to 78% and 49% in middle aged and old animals, respectively, compared to young animals (p LT 0.05). The specificity of the nuclear proteins-GRE interaction was demonstrated by competition experiments with unlabelled GRE. In a supershift assay, using the antibody BuGR2, it was shown that the GR proteins present in nuclear extracts have a high affinity for the GRE probe. The stabilities of the protein-DNA complexes were analysed and it was concluded that they changed during ageing.
T2  - Journal of the Serbian Chemical Society
T1  - Analysis of nuclear glucocorticoid receptor-DNA interaction in aged rat liver
VL  - 70
IS  - 5
SP  - 705
EP  - 712
DO  - 10.2298/JSC0505705V
ER  - 

@article{
author = "Vujčić, Miroslava T. and Terzić, N and Ristić-Fira, Aleksandra and Kanazir, Selma and Ruždijić, Sabera",
year = "2005",
abstract = "In order to contribute to the understanding of mechanisms by which regulatory proteins recognize genetic information stored in DNA, analyses of their interaction with specific nucleotides are usually performed. In this study, the electrophoretic mobility shift assay (EMSA) was applied to analyze the interaction of nuclear proteins from the liver of rats of different age i.e., young (3-month-old), middle-aged (12-month-old) and aged (24-month-old), with radioactively labelled synthetic oligonucleotide analogues, corresponding to GRE. The levels of GRE binding activity were assessed by quantitative densitometric scanning of the autoradiograms. The results showed statistically significant decreasing values of up to 78% and 49% in middle aged and old animals, respectively, compared to young animals (p LT 0.05). The specificity of the nuclear proteins-GRE interaction was demonstrated by competition experiments with unlabelled GRE. In a supershift assay, using the antibody BuGR2, it was shown that the GR proteins present in nuclear extracts have a high affinity for the GRE probe. The stabilities of the protein-DNA complexes were analysed and it was concluded that they changed during ageing.",
journal = "Journal of the Serbian Chemical Society",
title = "Analysis of nuclear glucocorticoid receptor-DNA interaction in aged rat liver",
volume = "70",
number = "5",
pages = "705-712",
doi = "10.2298/JSC0505705V"
}

Vujčić, M. T., Terzić, N., Ristić-Fira, A., Kanazir, S.,& Ruždijić, S.. (2005). Analysis of nuclear glucocorticoid receptor-DNA interaction in aged rat liver. in Journal of the Serbian Chemical Society, 70(5), 705-712.
https://doi.org/10.2298/JSC0505705V

Vujčić MT, Terzić N, Ristić-Fira A, Kanazir S, Ruždijić S. Analysis of nuclear glucocorticoid receptor-DNA interaction in aged rat liver. in Journal of the Serbian Chemical Society. 2005;70(5):705-712.
doi:10.2298/JSC0505705V .

Vujčić, Miroslava T., Terzić, N, Ristić-Fira, Aleksandra, Kanazir, Selma, Ruždijić, Sabera, "Analysis of nuclear glucocorticoid receptor-DNA interaction in aged rat liver" in Journal of the Serbian Chemical Society, 70, no. 5 (2005):705-712,
https://doi.org/10.2298/JSC0505705V . .

TY  - JOUR
AU  - Ruždijić, Sabera
AU  - Milošević, Jovan
AU  - Popović, Nataša M.
AU  - Pešić, Milica
AU  - Stojilkovic, M
AU  - Kanazir, Selma
AU  - Todorović, Danijela V.
AU  - Ristić-Fira, Aleksandra
AU  - Krstić-Demonacos, Marija
AU  - Kanazir, Selma
AU  - Rakić, Ljubisav
PY  - 2001
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2423
AB  - Tiazofurin and 8-Cl-cAMP are novel antineoplastic agents that have been shown to be effective against various cancer cells in vitro and in vivo. Through specific mechanisms of action they modulate the cellular signal transduction pathway, thereby causing growth inhibition, cell differentiation, apoptosis and downregulation of c-ras and c-myc gene expression. We examined the effects of 8-Cl-cAMP and tiazofurin, either separately or together, on apoptosis induction and c-fos and c-myc expression in melanoma cells. 8-Cl-cAMP and tiazofurin inhibited the growth of melanoma cells in a dose-responsive manner. Whether used separately or together, each agent induced apoptotic cell death. Apoptosis was accompanied by a marked inhibition of c-fos and c-mye gene expression. RT-PCR analysis showed that 8-Cl-cAMP, together with tiazofurin, promoted 61% and 75% decreases of c-myc and c-fos expression in melanoma cells respectively. These results clearly indicate that the combination of 8-Cl-cAMP and tiazofurin could provide a promising therapeutic approach for melanoma treatment.
T2  - Jugoslovenska Medicinska Biohemija
T1  - Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells
VL  - 20
IS  - 1
SP  - 9
EP  - 18
UR  - https://hdl.handle.net/21.15107/rcub_vinar_2423
ER  - 

@article{
author = "Ruždijić, Sabera and Milošević, Jovan and Popović, Nataša M. and Pešić, Milica and Stojilkovic, M and Kanazir, Selma and Todorović, Danijela V. and Ristić-Fira, Aleksandra and Krstić-Demonacos, Marija and Kanazir, Selma and Rakić, Ljubisav",
year = "2001",
abstract = "Tiazofurin and 8-Cl-cAMP are novel antineoplastic agents that have been shown to be effective against various cancer cells in vitro and in vivo. Through specific mechanisms of action they modulate the cellular signal transduction pathway, thereby causing growth inhibition, cell differentiation, apoptosis and downregulation of c-ras and c-myc gene expression. We examined the effects of 8-Cl-cAMP and tiazofurin, either separately or together, on apoptosis induction and c-fos and c-myc expression in melanoma cells. 8-Cl-cAMP and tiazofurin inhibited the growth of melanoma cells in a dose-responsive manner. Whether used separately or together, each agent induced apoptotic cell death. Apoptosis was accompanied by a marked inhibition of c-fos and c-mye gene expression. RT-PCR analysis showed that 8-Cl-cAMP, together with tiazofurin, promoted 61% and 75% decreases of c-myc and c-fos expression in melanoma cells respectively. These results clearly indicate that the combination of 8-Cl-cAMP and tiazofurin could provide a promising therapeutic approach for melanoma treatment.",
journal = "Jugoslovenska Medicinska Biohemija",
title = "Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells",
volume = "20",
number = "1",
pages = "9-18",
url = "https://hdl.handle.net/21.15107/rcub_vinar_2423"
}

Ruždijić, S., Milošević, J., Popović, N. M., Pešić, M., Stojilkovic, M., Kanazir, S., Todorović, D. V., Ristić-Fira, A., Krstić-Demonacos, M., Kanazir, S.,& Rakić, L.. (2001). Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells. in Jugoslovenska Medicinska Biohemija, 20(1), 9-18.
https://hdl.handle.net/21.15107/rcub_vinar_2423

Ruždijić S, Milošević J, Popović NM, Pešić M, Stojilkovic M, Kanazir S, Todorović DV, Ristić-Fira A, Krstić-Demonacos M, Kanazir S, Rakić L. Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells. in Jugoslovenska Medicinska Biohemija. 2001;20(1):9-18.
https://hdl.handle.net/21.15107/rcub_vinar_2423 .

Ruždijić, Sabera, Milošević, Jovan, Popović, Nataša M., Pešić, Milica, Stojilkovic, M, Kanazir, Selma, Todorović, Danijela V., Ristić-Fira, Aleksandra, Krstić-Demonacos, Marija, Kanazir, Selma, Rakić, Ljubisav, "Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells" in Jugoslovenska Medicinska Biohemija, 20, no. 1 (2001):9-18,
https://hdl.handle.net/21.15107/rcub_vinar_2423 .

TY  - JOUR
AU  - Djordjevic-Markovic, R
AU  - Radić, Olivera
AU  - Jelic, V
AU  - Radojčić, Marija
AU  - Rapic-Otrin, V
AU  - Ruždijić, Sabera
AU  - Krstić-Demonacos, Marija
AU  - Kanazir, Selma
AU  - Kanazir, Selma
PY  - 1999
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2305
AB  - The role of the glucocorticoid receptor (GR) in senescence was studied in rats of increasing age. Statistically significant changes in the number of GRs from rat liver were detected, whereas the affinity for the ligand triamcinolone acetonide (TA) did not change with increasing age, and was in the range of 1-2 nM. In all cases the number of receptors was lower in rats treated with hormone in vivo relative to untreated animals. In addition, we have found changes in GR activation, as measured by the binding to DNA cellulose in the mentioned age groups. Furthermore, expression of the glucocorticoid hormone (GH)-inducible gene, tyrosine amino transferase (TAT) also showed age-related alterations. We conclude that receptor function shows oscillatory changes during ageing. In addition, response to GH generally declines towards the older age. This. specific periodicity in functional characteristics of the GR may reconcile conflicting results about the receptor number and properties during the ageing process, and marks particular age at which individual organism shows the highest or the lowest sensitivity to the actions of GH. (C) 1999 Elsevier Science Inc. All rights reserved.
T2  - Experimental Gerontology
T1  - Glucocorticoid receptors in ageing rats
VL  - 34
IS  - 8
SP  - 971
EP  - 982
DO  - 10.1016/S0531-5565(99)00067-4
ER  - 

@article{
author = "Djordjevic-Markovic, R and Radić, Olivera and Jelic, V and Radojčić, Marija and Rapic-Otrin, V and Ruždijić, Sabera and Krstić-Demonacos, Marija and Kanazir, Selma and Kanazir, Selma",
year = "1999",
abstract = "The role of the glucocorticoid receptor (GR) in senescence was studied in rats of increasing age. Statistically significant changes in the number of GRs from rat liver were detected, whereas the affinity for the ligand triamcinolone acetonide (TA) did not change with increasing age, and was in the range of 1-2 nM. In all cases the number of receptors was lower in rats treated with hormone in vivo relative to untreated animals. In addition, we have found changes in GR activation, as measured by the binding to DNA cellulose in the mentioned age groups. Furthermore, expression of the glucocorticoid hormone (GH)-inducible gene, tyrosine amino transferase (TAT) also showed age-related alterations. We conclude that receptor function shows oscillatory changes during ageing. In addition, response to GH generally declines towards the older age. This. specific periodicity in functional characteristics of the GR may reconcile conflicting results about the receptor number and properties during the ageing process, and marks particular age at which individual organism shows the highest or the lowest sensitivity to the actions of GH. (C) 1999 Elsevier Science Inc. All rights reserved.",
journal = "Experimental Gerontology",
title = "Glucocorticoid receptors in ageing rats",
volume = "34",
number = "8",
pages = "971-982",
doi = "10.1016/S0531-5565(99)00067-4"
}

Djordjevic-Markovic, R., Radić, O., Jelic, V., Radojčić, M., Rapic-Otrin, V., Ruždijić, S., Krstić-Demonacos, M., Kanazir, S.,& Kanazir, S.. (1999). Glucocorticoid receptors in ageing rats. in Experimental Gerontology, 34(8), 971-982.
https://doi.org/10.1016/S0531-5565(99)00067-4

Djordjevic-Markovic R, Radić O, Jelic V, Radojčić M, Rapic-Otrin V, Ruždijić S, Krstić-Demonacos M, Kanazir S, Kanazir S. Glucocorticoid receptors in ageing rats. in Experimental Gerontology. 1999;34(8):971-982.
doi:10.1016/S0531-5565(99)00067-4 .

Djordjevic-Markovic, R, Radić, Olivera, Jelic, V, Radojčić, Marija, Rapic-Otrin, V, Ruždijić, Sabera, Krstić-Demonacos, Marija, Kanazir, Selma, Kanazir, Selma, "Glucocorticoid receptors in ageing rats" in Experimental Gerontology, 34, no. 8 (1999):971-982,
https://doi.org/10.1016/S0531-5565(99)00067-4 . .