Title:GABAergic Agonists Modulate the Glutamate Release from Frontal Cortex Synaptosomes of Rats with Experimental Autoimmune Encephalomyelitis
Volume: 14
Issue: 2
Author(s): Nicolás Fernández Hurst, Natalí L. Chanaday and German A. Roth
Affiliation:
Keywords:
Autoimmunity, multiple sclerosis, synapsins, benzodiazepines, glutamate release, GABA
Abstract: Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating
disease that mimics many of the clinical and pathological features of multiple sclerosis. We have
previously described a significant diminution in the GABAergic regulation of glutamate release from
synaptosomes of EAE rats isolated during the acute stage of the disease. In order to explore the
possible metabolic pathways responsible for this alteration, in this work we evaluate the direct effect
of different GABAergic agonists on the glutamate release and concomitant synapsin I phosphorylation
in synaptosomes from the frontal cortex of control and EAE animals. The results show that GABA as well as the GABA
receptor agonists Muscimol (GABAA agonist) and Baclofen (GABAB agonist) caused a decrease in glutamate release in
control rats paralleled by a similar reduction in synapsin I phosphorylation. Meanwhile synaptosomes from EAE animals
are responsive only to Baclofen with respect to nontreated EAE synaptosomes, since glutamate release from the
synaptosomes treated with Muscimol was similar to that observed in EAE rat synaptosomes which was already reduced as
consequence of the disease. In the case of the benzodiazepines Diazepam and Clonazepam (GABAA allosteric agonists),
both of them induced a reduction in glutamate release in synaptosomes from the CFA rats, effect that was only observed
in synaptosomes of EAE rats treated with Clonazepam. In all cases both benzodiazepines showed a higher effect on
synapsin I phosphorylation than in glutamate release. These results indicate that the extent of GABAergic modulation of
presynaptic terminals depends on the type of agonist employed and this regulation is altered in the frontal cortex during
the acute phase of EAE with respect to control animals.
