2 research outputs found
Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis
Aims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE.
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry.
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency,
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and
IL-1Ī² expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more
pronounced in aged than in young rats
Infrared radiation from cage bedding moderates rat inflammatory and autoimmune responses in collagenāinduced arthritis
Abstract: The development of collagen type II (CII)-induced arthritis (CIA), a model of rheumatoid arthritis, in rats housed in cages with bedding composed of Celliant fibres containing ceramic particles, which absorb body heat and re-emit the energy back to the body in the form of infrared radiation (+IRF rats), and those housed in cages with standard wooden shaving bedding (āIRF control rats) was examined. The appearance of the first signs of CIA was postponed, while the disease was milder (judging by the arthritic score, paw volume, and burrowing behaviour) inā+IRF compared with āIRF rats. This correlated with a lower magnitude of serum anti-CII IgG antibody levels inā+IRF rats, and lower production level of IL-17, the Th17 signature cytokine, in cultures of their paws. This could be partly ascribed to impaired migration of antigen-loaded CD11bā+ādendritic cells and their positioning within lymph nodes inā+IRF rats reflecting diminished lymph node expression of CCL19 /CCL21. Additionally, as confirmed in rats with carrageenan-induced paw inflammation (CIPI), the infrared radiation from Celliant fibres, independently from immunomodulatory effects, exerted anti-inflammatory effects (judging by a shift in pro-inflammatory mediator to anti-inflammatory/immunoregulatory mediator ratio towards the latter in paw cultures) and ameliorated burrowing behaviour in CIA rats