Inhibitory role of diazepam on autoimmune inflammation in rats with experimental autoimmune encephalomyelitis

BIBOLINI MJ; CHANADAY RICAGNI NL; BÁEZ NS; DEGANO AL; MONFERRÁN CG; ROTH GA

Huerta Grande, Córdoba (Argentina)

Congreso; XXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN).; 2011

Sociedad Argentina de Investigación en Neurociencias (SAN).

Glutamate and GABA are the respective main excitatory and inhibitory neurotransmitters in the central nervous system and both may be involved in the neuronal dysfunction in neurodegenerative conditions. We have recently found that glutamate release was decreased in isolated synaptosomes from the rat cerebral cortex during the development of experimental autoimmune encephalomyelitis (EAE). We have evaluated the relevance of the GABAergic system in EAE by treating rats challenged for the disease with the GABA agonist diazepam. Administration of diazepam during six days starting at day 6 or 11 after EAE induction leads to a marked decrease of the disease incidence and histological signs in spinal cord. Cellular reactivity and antibody responses against the encephalitogenic myelin basic protein were also diminished. Beyond the effects of diazepam on the autoimmune, inflammatory response, we report also a positive effect on neurotransmission. Treatment with diazepam inhibited the previously described reduction in glutamate release in the frontal cortex synaptosomes from EAE animals. These data suggest that an endogenous inhibitory GABAergic system within the immune system is involved in the diazepam effect on EAE and indicate that increasing GABAergic activity potently ameliorate EAE.