Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
Ivana Ćuruvija
Department of Research and Development, Institute of Virology, Vaccines and Sera, Torlak, 11000 Belgrade, Serbia
Veljko Blagojević
Department of Research and Development, Institute of Virology, Vaccines and Sera, Torlak, 11000 Belgrade, Serbia
Jelica Grujić-Milanović
Institute for Medical Research, National Institute of the Republic of Serbia, Department of Cardiovascular Research, University of Belgrade, 11000 Belgrade, Serbia
Ivana Prijić
Department of Research and Development, Institute of Virology, Vaccines and Sera, Torlak, 11000 Belgrade, Serbia
Tatjana Radosavljević
Institute of Pathological Physiology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Janko Samardžić
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Milica Radosavljevic
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Radmila Janković
Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Jasmina Djuretić
Department of Pathobiology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
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.