Inhibition of Ca2+-dependent glutamate release from cerebral cortex synaptosomes of rats with experimental autoimmune encephalomyelitis

Aldo Alejandro Vilcaes, Gabriela Furlan, German A. Roth

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 Ca2+-dependent but not the Ca2+-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 Ca2+ using fura-2-acetoxymethyl ester revealed that the inhibition of glutamate release could not be attributed to a reduction in voltage-dependent Ca2+ 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 Ca2+-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 Ca2+.

Original languageEnglish (US)
Pages (from-to)881-890
Number of pages10
JournalJournal of Neurochemistry
Volume108
Issue number4
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

Fingerprint

Autoimmune Experimental Encephalomyelitis
Synaptosomes
Cerebral Cortex
Rats
Glutamic Acid
Multiple Sclerosis
Animals
Neurotransmitter Agents
Synapsins
4-Aminopyridine
Phosphorylation
Ionomycin
Deregulation
Fura-2
Acute Disease
Metabolism
Esters
Animal Models
Electric potential
Proteins

Keywords

  • Calcium influx
  • Glutamate release
  • Synapsin
  • Synapsin phosphorylation
  • Synaptosomes

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Inhibition of Ca2+-dependent glutamate release from cerebral cortex synaptosomes of rats with experimental autoimmune encephalomyelitis. / Vilcaes, Aldo Alejandro; Furlan, Gabriela; Roth, German A.

In: Journal of Neurochemistry, Vol. 108, No. 4, 01.02.2009, p. 881-890.

Research output: Contribution to journalArticle

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