TY  - JOUR
AU  - Bufan, Biljana
AU  - Ćuruvija, Ivana
AU  - Blagojević, Veljko
AU  - Grujić-Milanović, Jelica
AU  - Prijić, Ivana
AU  - Radosavljević, Tatjana
AU  - Samardžić, Janko
AU  - Radosavljevic, Milica
AU  - Janković, Radmila
AU  - Djuretić, Jasmina
PY  - 2024
UR  - http://intor.torlakinstitut.com/handle/123456789/867
AB  - Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.
PB  - MDPI
T2  - Biomedicines
T2  - Biomedicines
T1  - NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats
IS  - 4
SP  - 717
VL  - 12
DO  - 10.3390/biomedicines12040717
ER  - 

@article{
author = "Bufan, Biljana and Ćuruvija, Ivana and Blagojević, Veljko and Grujić-Milanović, Jelica and Prijić, Ivana and Radosavljević, Tatjana and Samardžić, Janko and Radosavljevic, Milica and Janković, Radmila and Djuretić, Jasmina",
year = "2024",
abstract = "Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.",
publisher = "MDPI",
journal = "Biomedicines, Biomedicines",
title = "NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats",
number = "4",
pages = "717",
volume = "12",
doi = "10.3390/biomedicines12040717"
}

Bufan, B., Ćuruvija, I., Blagojević, V., Grujić-Milanović, J., Prijić, I., Radosavljević, T., Samardžić, J., Radosavljevic, M., Janković, R.,& Djuretić, J.. (2024). NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats. in Biomedicines
MDPI., 12(4), 717.
https://doi.org/10.3390/biomedicines12040717

Bufan B, Ćuruvija I, Blagojević V, Grujić-Milanović J, Prijić I, Radosavljević T, Samardžić J, Radosavljevic M, Janković R, Djuretić J. NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats. in Biomedicines. 2024;12(4):717.
doi:10.3390/biomedicines12040717 .

Bufan, Biljana, Ćuruvija, Ivana, Blagojević, Veljko, Grujić-Milanović, Jelica, Prijić, Ivana, Radosavljević, Tatjana, Samardžić, Janko, Radosavljevic, Milica, Janković, Radmila, Djuretić, Jasmina, "NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats" in Biomedicines, 12, no. 4 (2024):717,
https://doi.org/10.3390/biomedicines12040717 . .

TY  - CONF
AU  - Ćuruvija, Ivana
AU  - Bufan, Biljana
AU  - Đorović, Emilija
AU  - Blagojević, Veljko
AU  - Grujić-Milanović, Jelica
AU  - Marković, Milica
AU  - Djuretić, Jasmina
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/674
AB  - Aims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE.
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry.
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency,
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and
IL-1β expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more
pronounced in aged than in young rats.
C3  - FENS Forum Book of Abstracts, Paris
T1  - Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis
SP  - S05-250
UR  - https://hdl.handle.net/21.15107/rcub_intor_674
ER  - 

@conference{
author = "Ćuruvija, Ivana and Bufan, Biljana and Đorović, Emilija and Blagojević, Veljko and Grujić-Milanović, Jelica and Marković, Milica and Djuretić, Jasmina",
year = "2022",
abstract = "Aims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE.
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry.
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency,
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and
IL-1β expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more
pronounced in aged than in young rats.",
journal = "FENS Forum Book of Abstracts, Paris",
title = "Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis",
pages = "S05-250",
url = "https://hdl.handle.net/21.15107/rcub_intor_674"
}

Ćuruvija, I., Bufan, B., Đorović, E., Blagojević, V., Grujić-Milanović, J., Marković, M.,& Djuretić, J.. (2022). Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis. in FENS Forum Book of Abstracts, Paris, S05-250.
https://hdl.handle.net/21.15107/rcub_intor_674

Ćuruvija I, Bufan B, Đorović E, Blagojević V, Grujić-Milanović J, Marković M, Djuretić J. Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis. in FENS Forum Book of Abstracts, Paris. 2022;:S05-250.
https://hdl.handle.net/21.15107/rcub_intor_674 .

Ćuruvija, Ivana, Bufan, Biljana, Đorović, Emilija, Blagojević, Veljko, Grujić-Milanović, Jelica, Marković, Milica, Djuretić, Jasmina, "Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis" in FENS Forum Book of Abstracts, Paris (2022):S05-250,
https://hdl.handle.net/21.15107/rcub_intor_674 .