GLT-1 down-regulation induced by clozapine in rat frontal cortex is associated with synaptophysin up-regulation

Luca Bragina, Marcello Melone, Giorgia Fattorini, Monica Torres-Ramos, Ainara Vallejo-Illarramendi, Carlos Matute, Fiorenzo Conti

Research output: Contribution to journalArticle

Abstract

In rat frontal cortex, extracellular levels of glutamate are raised by the anti-psychotic drug clozapine. We have recently shown that a significant reduction in the levels of the glutamate transporter GLT-1 may be one of the mechanisms responsible for this elevation. Here we studied whether GLT-1 down-regulation induced by chronic clozapine treatment is associated with changes in the expression of synaptophysin, synaptosome-associated protein of 25 kDa (SNAP-25) and vesicular glutamate transporter 1 (VGLUT1), three major presynaptic proteins involved in neurotransmitter release. Quantitative high-resolution confocal microscopy studies in vivo showed that GLT-1 down-regulation is closely associated with a significant increase in synaptophysin, but not SNAP-25 and VGLUT1, expression. This was confirmed in vitro studies, and in western blotting studies of synaptophysin, SNAP-25 and VGLUT1. In addition, our results show that, following clozapine treatment, synaptophysin expression increases in the very cortical regions in which GLT-1 expression is down-regulated. These findings suggest that part of the effects of clozapine may be exerted via an action on the presynaptic machinery involved in neurotransmitter release.

Original languageEnglish
Pages (from-to)134-141
Number of pages8
JournalJournal of Neurochemistry
Volume99
Issue number1
DOIs
Publication statusPublished - Oct 2006

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Keywords

  • Antipsychotics
  • Exocytosis
  • Glutamate
  • Glutamate transport
  • Schizophrenia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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