Premium
GLT‐1 down‐regulation induced by clozapine in rat frontal cortex is associated with synaptophysin up‐regulation
Author(s) -
Bragina Luca,
Melone Marcello,
Fattorini Giorgia,
TorresRamos Monica,
VallejoIllarramendi Ainara,
Matute Carlos,
Conti Fiorenzo
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04030.x
Subject(s) - synaptophysin , neurotransmitter , glutamate receptor , neuroscience , synaptosome , biology , autoreceptor , reuptake , synaptic vesicle , chemistry , microbiology and biotechnology , medicine , immunohistochemistry , central nervous system , biochemistry , receptor , antagonist , vesicle , membrane , serotonin
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.