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Clozapine reduces GLT‐1 expression and glutamate uptake in astrocyte cultures
Author(s) -
VallejoIllarramendi Ainara,
TorresRamos Mónica,
Melone Marcello,
Conti Fiorenzo,
Matute Carlos
Publication year - 2005
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20172
Subject(s) - astrocyte , glutamate receptor , clozapine , biology , transporter , neuroscience , pharmacology , excitatory amino acid transporter , cerebral cortex , schizophrenia (object oriented programming) , neuroglia , biochemistry , central nervous system , psychology , receptor , psychiatry , gene
Abstract To test the hypothesis that clozapine‐induced reduction of glutamate transporter‐1 (GLT‐1) expression is mediated by astrocytes, we studied the effects of clozapine on Glu transporters and Glu uptake in primary astrocyte cultures of the cerebral cortex. Astrocyte cultures treated for 48 h with clozapine exhibited a reduction in GLT‐1 levels of about 50%, whereas glutamate–aspartate transporter (GLAST) levels remained unchanged. Glu uptake was also lowered, and this reduction was dose‐dependent. Our findings indicate that clozapine reduces GLT‐1 expression and function by a mechanism that directly involves astrocytes. A better understanding of the molecular events by which antipsychotics regulate Glu uptake can contribute to identify new targets for the treatment of schizophrenia. © 2005 Wiley‐Liss, Inc.