Involvement of the GABAergic system in the glutamate release modulation of frontal cortex synaptosomes of rats with experimental autoimmune encephalomyelitis (EAE)

FERNÁNDEZ HURST, NICOLÁS; ROTH GERMAN A.

Huerta Grande, Córdoba

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia (SAN); 2012

SAN

EAE is a model that mimics many of the clinical and pathological features of multiple sclerosis. GABA is an essential neurotransmitter involved in the maintenance of neuronal homeostasis, in this work we evaluate the effect of GABAergic agonists in the modulation of glutamate release of control and EAE rat frontal cortex synaptosomes and their effect on the synapsin I phosphorylation. The results show that GABA agonists contribute to a decrease in glutamate release and synapsin phosphorylation on site P-3. For GABA, Muscimol (GABAA-agonist), Baclofen (GABAB-agonist), Gabapentin (calcium channel blocker), exists a correlation between the decrease in synapsin phosphorylation and Ca+2-dependent glutamate release. In the case of the benzodiazepines Diazepam and Clonazepam, GABAA allosteric agonists, the decrease in synapsin phosphorylation is higher than the effect in glutamate release. The effect of the GABA agonists in some cases was partially blocked by picrotoxin. In conclusion, these results indicate that the GABAergic system modulation is altered in the acute phase of EAE depending on the activated pathway.