Recently we found that the glutamate release and synapsin I phosphorylation were decreased in synaptosomes from rat cerebral cortex during the development of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. In order to evaluate the events that may affect neuronal function in EAE synaptosomes, we analyzed the modulation of the GABAergic system on the glutamate release and synapsin phosphorilation, and the flunitrazepam sensitive-GABAA receptor density. We describe alterations of the GABAergic system of frontal cortex synaptosomes from EAE animals. In contrast to control animals where GABA induced a decrease in the glutamate release, which was abolished by picrotoxin, synaptosomes from EAE rats showed a loss in the inhibition of the glutamate release mediated by GABA. Furthermore, the flunitrazepam sensitive-GABAA receptor density was decreased during the acute stage of the disease in synaptosomes from EAE rats. On the other hand, it was studied if in EAE cortical synaptosomes GABA inhibited synapsin I phosphorylation via Ca2+/calmodulin, which in turn decreased the glutamate release. The changes observed in the GABAergic inhibition were reverted in cortical synaptosomes from recovered EAE animals. These results suggest that the diminution of the flunitrazepam sensitive-GABAA receptor density could explain the observed failure of the GABAergic regulation on the glutamate release of synaptosomes from EAE rats, and could contribute to clinical symptoms and disease progression.
