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Clozapine reduces GLT-1 expression and glutamate uptake in astrocyte cultures

✍ Scribed by Ainara Vallejo-Illarramendi; Mónica Torres-Ramos; Marcello Melone; Fiorenzo Conti; Carlos Matute


Book ID
102225185
Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
463 KB
Volume
50
Category
Article
ISSN
0894-1491

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✦ Synopsis


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. V


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✍ Carlos Matute; Marcello Melone; Ainara Vallejo-Illarramendi; Fiorenzo Conti 📂 Article 📅 2004 🏛 John Wiley and Sons 🌐 English ⚖ 254 KB

## Abstract To verify whether altered glial glutamate uptake contributes to the reduced efficacy of glutamatergic transmission reported in the prefrontal cortex of schizophrenics, we studied the expression of GLT‐1, the transporter responsible for most glutamate transport, in autoptic samples of pr