NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats
Authors
Bufan, Biljana![](/themes/MirageInTOR/images/orcid.png)
Ćuruvija, Ivana
![](/themes/MirageInTOR/images/orcid.png)
Blagojević, Veljko
![](/themes/MirageInTOR/images/orcid.png)
Grujić-Milanović, Jelica
Prijić, Ivana
![](/themes/MirageInTOR/images/orcid.png)
Radosavljević, Tatjana
Samardžić, Janko
Radosavljevic, Milica
Janković, Radmila
Djuretić, Jasmina
Article (Published version)
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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.
Keywords:
aging / EAE / memantine / multiple sclerosis / NMDARsSource:
Biomedicines, 2024, 12, 4, 717-Publisher:
- MDPI
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200177 (Immunology Research Centre 'Branislav Janković' Torlak, Belgrade) (RS-MESTD-inst-2020-200177)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200015 (University of Belgrade, Institute for Medical Research) (RS-MESTD-inst-2020-200015)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200110 (University of Belgrade, Faculty of Medicine) (RS-MESTD-inst-2020-200110)
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TorlakTY - 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 . .