Participation of the GABAergic system on the glutamate release of frontal cortex synaptosomes from wistar rats with experimental autoimmune encephalomyelitis

MARIANA P. CID; A. ALEJANDRO VILCAES; LUCÍA L. RUPIL; NANCY A. SALVATIERRA; GERMAN A. ROTH

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2011 vol. 189 p. 337 - 344

0306-4522

Recently we found that the glutamate release was decreased in synaptosomes from rat cerebral cortex during the development of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. Various reports have shown a deficit in the expression of proteins associated with GABAergic neurotransmission in neocortex of patients with multiple sclerosis and it has also been described that the activation of GABAA receptors leads to an inhibition of glutamate release. Therefore, in order to evaluate the events that may affect neuronal function in EAE synaptosomes, we analyzed the participation of the GABAergic system on the glutamate release and the flunitrazepam sensitive-GABAA receptor density. We describe alterations of the GABAergic system of frontal cortex synaptosomes from EAE animals. GABA induced a decrease in the 4-aminopyridine-evoked glutamate release in control synaptosomes, which was abolished by picrotoxin (a GABAA antagonist). In contrast 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. We also observed a loss of inhibition on the Ca2+-dependent phosphorylation of synapsin I mediated by GABA in nerve terminal from EAE animals which could explain the loss of GABAergic regulation on evoked glutamate release. The changes observed in the GABAA receptor density as well as the loss GABAergic inhibition of glutamate release were partially 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.