Inhibition of Ca(2+)-dependent glutamate release from cerebral cortex synaptosomes of rats with experimental autoimmune encephalomyelitis.
Several pathological studies have revealed a prominent involvement of the cerebral cortex in patients with multiple sclerosis (MS). In order to better understand the events that lead to the progressive neuronal dysfunction in MS, herein we explore the contribution of the glutamatergic release in cerebral cortex synaptosomes isolated from rats with experimental autoimmune encephalomyelitis, an animal model reproducing many features of MS. We found that the Ca(2+)-dependent but not the Ca(2+)-independent glutamate release induced by KCl and 4-aminopyridine was significantly decreased during the acute stage of the disease. This inhibited release coincides with the onset of the clinical signs and after 24 h tends to recover the level of the control animals. The results also showed an inhibition of the glutamate release stimulated by ionomycin. When the animals were totally recovered from clinical signs, the neurotransmitter release stimulated by the different inductors was similar to the controls. Examination of the cytosolic Ca(2+) using fura-2-acetoxymethyl ester revealed that the inhibition of glutamate release could not be attributed to a reduction in voltage-dependent Ca(2+) influx. However, this inhibition was concomitant with a lower phosphorylation of synapsin I at P-site1. Our results show that the inhibition observed on the Ca(2+)-dependent neurotransmitter release from cerebral cortex synaptosomes in experimental autoimmune encephalomyelitis is specific and correlates with the beginning of the clinical disease. Moreover, they suggest an alteration in the metabolism of proteins involved in the vesicular glutamate release more than a deregulation in the influx of cytosolic Ca(2+).
Vilcaes
Aldo Alejandro
AA
Centro de Investigaciones en Química Biológica de Córdoba, Departamento de Química Biológica, Universidad Nacional de Córdoba, Argentina.
Furlan
Gabriela
G
Roth
German A
GA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology*; D010766:Phosphorylation; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016704:Synapsins / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D015220:Calcium Channels; D026902:Potassium Channel Blockers; D011500:Protein Synthesis Inhibitors; D016704:Synapsins; D018698:Glutamic Acid; D011189:Potassium Chloride; D002118:Calcium