NMDA Receptor Antagonist Memantine AmelioratesExperimental Autoimmune Encephalomyelitis in Aged Rats

Aging is closely related to the main aspects of multiple sclerosis (MS). The average age ofthe MS population is increasing and the number of elderly MS patients is expected to increase. Inaddition to neurons,N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronalcells, such as immune cells. The aim of this study was to investigate the role of NMDARs inexperimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and agedDark Agoutirats from day7 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 ofthe fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent inaged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expressionin brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advancedoxidation protein products in brain tissue were consistent with previous results. Overall, our resultssuggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.