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 . .