Inhibition of Ca2+ dependent glutamate release in cerebral cortex synaptosomes of rats with EAE

A. ALEJANDRO VILCAES; GABRIELA FURLAN,; GERMAN A. ROTH

Mar del Plata, Buenos Aires

Congreso; XLIII Reunión Nacional de la Sociedad Argentina de Investigación en Bioquímica y Biología Celular (SAIB).; 2007

Sociedad Argentina de Investigación en Bioquímica y Biología Celular (SAIB).

In order to better understand the mechanism leading to progressive neurological deficit in multiple sclerosis, herein we explore the contribution of glutamate release in the cerebral cortex synaptosomes isolated from experimental autoimmune encephalomyelitis (EAE) animals. Active disease was induced in rats by intradermal injection with complete Freund?s adjuvant alone (control group) or containing bovine myelin (EAE group). The evoked neurotransmitter release was monitored using an enzyme-linked fluorometric assay. The total Ca²⁺ dependent glutamate release induced by KCl and 4-aminopyridine, but not by ionomycin was significatively decreased during the acute stage of the disease. When the animals were totally recovered from clinical signs, the neurotransmitter release stimulated by all the inductors were similar to controls. No significant differences were found in cytosolic Ca²⁺ measured using Fura-2. The alteration of neurotransmitter release was concomitant with an inhibition of synapsin phosphorylation. Ours results shown that the inhibition observed on the Ca²⁺ dependent neurotransmitter release from cerebral cortex synaptosomes in EAE is specific and correlates with the course of the clinical disease. Moreover, they suggest an alteration in the metabolism of proteins involved in the vesicular glutamate release more than a desbalance in the influx of cytosolic Ca²⁺.