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  - 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  - Vasović, Dolika D.
AU  - Vesković, Milena
AU  - Šutulović, Nikola
AU  - Hrnčić, Dragan
AU  - Takić, Marija
AU  - Jerotić, Đurđa
AU  - Matić, Marija
AU  - Stanojlović, Olivera
AU  - Ivković, Sanja
AU  - Jovanović Macura, Irena
AU  - Mladenović, Dušan
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11076
AB  - The aim of our study was to investigate the effects of a shortened daily photoperiod on anxiety-like behaviour, brain oxidative stress, lipid status and fatty acid composition of serum lipids in a streptozotocin (STZ)-induced model of diabetes mellitus in rats. Male Wistar rats were divided into the following groups: first group—control group (C12/12); second group—diabetic group (DM12/12; 100 mg/kg STZ); third group—control group exposed to a light/dark cycle 6/18 h (C6/18); fourth group—diabetic group exposed to a light/dark cycle 6/18 h (DM6/18). Anxiety-like behaviour was tested three weeks following STZ injection by elevated plus maze (EPM) and open-field test (OFT). Oxidative stress parameters were measured in the cortex, hippocampus and thalamus, while lipid status and fatty acid methyl esters (FAMEs) were measured in the serum. Both EPM and OFT showed a lower degree of anxiety-like behaviour in the DM6/18 vs. DM12/12 group. Lipid peroxidation in the cortex, hippocampus and thalamus was significantly lower in the DM6/18 vs. DM12/12 group (p < 0.05), associated with an increased level of antioxidant enzymes and protein thiols in the cortex and thalamus. In the DM6/18 group, oleic, vaccenic, dihomo-γ-linolenic and docosahexaenoic acid concentrations were significantly higher in comparison to the DM12/12 group. A shortened daily photoperiod alleviates anxiety-like behaviour in diabetic rats by reduced lipid peroxidation and changes in the serum fatty acids profile.
T2  - Journal of Personalized Medicine
T1  - Shortened Daily Photoperiod Alleviates Anxiety-like Behaviour by Antioxidant Effect and Changes Serum Fatty Acid Profile in Diabetic Rats
VL  - 13
IS  - 5
SP  - 744
DO  - 10.3390/jpm13050744
ER  - 

@article{
author = "Vasović, Dolika D. and Vesković, Milena and Šutulović, Nikola and Hrnčić, Dragan and Takić, Marija and Jerotić, Đurđa and Matić, Marija and Stanojlović, Olivera and Ivković, Sanja and Jovanović Macura, Irena and Mladenović, Dušan",
year = "2023",
abstract = "The aim of our study was to investigate the effects of a shortened daily photoperiod on anxiety-like behaviour, brain oxidative stress, lipid status and fatty acid composition of serum lipids in a streptozotocin (STZ)-induced model of diabetes mellitus in rats. Male Wistar rats were divided into the following groups: first group—control group (C12/12); second group—diabetic group (DM12/12; 100 mg/kg STZ); third group—control group exposed to a light/dark cycle 6/18 h (C6/18); fourth group—diabetic group exposed to a light/dark cycle 6/18 h (DM6/18). Anxiety-like behaviour was tested three weeks following STZ injection by elevated plus maze (EPM) and open-field test (OFT). Oxidative stress parameters were measured in the cortex, hippocampus and thalamus, while lipid status and fatty acid methyl esters (FAMEs) were measured in the serum. Both EPM and OFT showed a lower degree of anxiety-like behaviour in the DM6/18 vs. DM12/12 group. Lipid peroxidation in the cortex, hippocampus and thalamus was significantly lower in the DM6/18 vs. DM12/12 group (p < 0.05), associated with an increased level of antioxidant enzymes and protein thiols in the cortex and thalamus. In the DM6/18 group, oleic, vaccenic, dihomo-γ-linolenic and docosahexaenoic acid concentrations were significantly higher in comparison to the DM12/12 group. A shortened daily photoperiod alleviates anxiety-like behaviour in diabetic rats by reduced lipid peroxidation and changes in the serum fatty acids profile.",
journal = "Journal of Personalized Medicine",
title = "Shortened Daily Photoperiod Alleviates Anxiety-like Behaviour by Antioxidant Effect and Changes Serum Fatty Acid Profile in Diabetic Rats",
volume = "13",
number = "5",
pages = "744",
doi = "10.3390/jpm13050744"
}

Vasović, D. D., Vesković, M., Šutulović, N., Hrnčić, D., Takić, M., Jerotić, Đ., Matić, M., Stanojlović, O., Ivković, S., Jovanović Macura, I.,& Mladenović, D.. (2023). Shortened Daily Photoperiod Alleviates Anxiety-like Behaviour by Antioxidant Effect and Changes Serum Fatty Acid Profile in Diabetic Rats. in Journal of Personalized Medicine, 13(5), 744.
https://doi.org/10.3390/jpm13050744

Vasović DD, Vesković M, Šutulović N, Hrnčić D, Takić M, Jerotić Đ, Matić M, Stanojlović O, Ivković S, Jovanović Macura I, Mladenović D. Shortened Daily Photoperiod Alleviates Anxiety-like Behaviour by Antioxidant Effect and Changes Serum Fatty Acid Profile in Diabetic Rats. in Journal of Personalized Medicine. 2023;13(5):744.
doi:10.3390/jpm13050744 .

Vasović, Dolika D., Vesković, Milena, Šutulović, Nikola, Hrnčić, Dragan, Takić, Marija, Jerotić, Đurđa, Matić, Marija, Stanojlović, Olivera, Ivković, Sanja, Jovanović Macura, Irena, Mladenović, Dušan, "Shortened Daily Photoperiod Alleviates Anxiety-like Behaviour by Antioxidant Effect and Changes Serum Fatty Acid Profile in Diabetic Rats" in Journal of Personalized Medicine, 13, no. 5 (2023):744,
https://doi.org/10.3390/jpm13050744 . .