NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats

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, -methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as...

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Published in:Biomedicines 2024-04, Vol.12 (4), p.717
Main Authors: Bufan, Biljana, Ćuruvija, Ivana, Blagojević, Veljko, Grujić-Milanović, Jelica, Prijić, Ivana, Radosavljević, Tatjana, Samardžić, Janko, Radosavljevic, Milica, Janković, Radmila, Djuretić, Jasmina
Format: Article
Language:English
Subjects:
Age
Aging
Animals
Apoptosis
Brain research
CD4 antigen
CX3CR1 protein
EAE
Encephalomyelitis
Experimental allergic encephalomyelitis
Flow cytometry
Fractalkine
Gene expression
Geriatrics
Glutamic acid receptors
Glutamic acid receptors (ionotropic)
Immunization
Inflammation
Life expectancy
Lymphocytes
Lymphocytes T
Memantine
Multiple sclerosis
N-Methyl-D-aspartic acid receptors
Nervous system agents
NMDARs
Older people
Paralysis
Pathogenesis
R&D
Research & development
RNA
Spinal cord
Superoxide
Superoxide anions
T cells
Vaccines
Virology
Young adults
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Summary: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, -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 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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines12040717