Memantine reduces the expression of IFN-gamma and IL-17 by CD4+ t cells in aged EAE rats

Abstract

The average age of patients with multiple sclerosis (MS) has risen in recent decades. The incidence of late-onset MS has also increased. More than half of people living with an MS diagnosis are over 55. Ageing affects the composition and function of N-methyl-D-aspartate receptors (NMDARs), regardless of whether they are expressed on neuronal or immune cells. The aim of this study was to investigate the effects of memantine, a non-competitive NMDAR antagonist, on CD4 + T lymphocytes in young and aged rats immunized for experimental autoimmune encephalomyelitis (EAE). Memantine was administered by oral gavage to 3- and 24-month-old female Dark Agouti rats for 7 consecutive days from the first day post-immunization (dpi) or from the 7 th dpi. Mononuclear cells were isolated from the lymph nodes draining the site of immunization or the spinal cord and analysed by flow cytometry. A histopathologic analysis of the spinal cord was performed. Memantine administration more effectively reduced the mean neurological score and histological score in aged rats. Memantine reduced the expression of IFN-gamma and IL-17 by CD4 + T lymphocytes derived from draining lymph nodes or the spinal cord to a greater extent in aged rats. On the other hand, there was no difference in apoptosis of CD4 + T lymphocytes between control and memantine-treated young rats, whereas apoptosis of these cells was significantly reduced in memantine-treated aged rats. NMDARs have a greater effect on IFN-gamma and IL-17 synthesis by CD4 + T cells and apoptosis of these cells in aged than in young EAE rats