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Titolo:
The expression of glutamate transporter GLT-1 in the rat cerebral cortex is down-regulated by the antipsychotic drug clozapine
Autore:
Melone, M; Vitellaro-Zuccarello, L; Vallejo-Illarramendi, A; Perez-Samartin, A; Matute, C; Cozzi, A; Pellegrini-Giampietro, DE; Rothstein, JD; Conti, F;
Indirizzi:
Univ Ancona, Ist Fisiol Umana, I-60020 Ancona, Italy Univ Ancona Ancona Italy I-60020 Ist Fisiol Umana, I-60020 Ancona, Italy Univ Milan, Dipartimento Fisiol & Biochim Gen, I-20133 Milan, Italy Univ Milan Milan Italy I-20133 isiol & Biochim Gen, I-20133 Milan, Italy Univ Pais Vasco, Dept Neurociencias, Leioa 48940, Vizcaya, Spain Univ PaisVasco Leioa Vizcaya Spain 48940 as, Leioa 48940, Vizcaya, Spain Univ Florence, Dipartimento Farmacol Preclin & Clin, I-50139 Florence, Italy Univ Florence Florence Italy I-50139 lin & Clin, I-50139 Florence, Italy Johns Hopkins Hosp, Dept Neurol, Baltimore, MD 21287 USA Johns Hopkins Hosp Baltimore MD USA 21287 Neurol, Baltimore, MD 21287 USA
Titolo Testata:
MOLECULAR PSYCHIATRY
fascicolo: 4, volume: 6, anno: 2001,
pagine: 380 - 386
SICI:
1359-4184(200107)6:4<380:TEOGTG>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEDIAL PREFRONTAL CORTEX; MESSENGER-RNA; RECEPTOR EXPRESSION; SCHIZOPHRENIA; HALOPERIDOL; DOPAMINE; MODEL; BRAIN; LOCALIZATION; MECHANISMS;
Keywords:
glutamate; glutamate uptake; neuroleptics; transporter regulation; synaptic transmission; schizophrenia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Conti, F Univ Ancona, Ist Fisiol Umana, Via Tronto 10-A,Torrette Ancona 1,I-60020 Ancona, Italy Univ Ancona Via Tronto 10-A,Torrette Ancona 1 Ancona Italy I-60020
Citazione:
M. Melone et al., "The expression of glutamate transporter GLT-1 in the rat cerebral cortex is down-regulated by the antipsychotic drug clozapine", MOL PSYCHI, 6(4), 2001, pp. 380-386

Abstract

We show here that clozapine, a beneficial antipsychotic, down-regulates the expression of the glutamate transporter GLT-1 in the rat cerebral cortex,thereby reducing glutamate transport and raising extracellular glutamate levels. Clozapine treatment (25-35 mg kg(-1) day(-1) orally) reduced GLT-1 immunoreactivity in several brain regions after 3 weeks; this effect was most prominent after 9 weeks and most evident in the frontal cortex. GLT-1 protein levels were reduced in the cerebral cortex of treated rats compared with controls and were more severely affected in the anterior (71.9 +/- 4.5%)than in the posterior (53.2 +/- 15.4%) cortex. L-[H-3]-glutamate uptake inXenopus laevis oocytes injected with mRNA extracted from the anterior cerebral cortex of rats treated for 9 weeks was remarkably reduced (to 30.6 +/-8.6%) as compared to controls. In addition, electrophysiological recordings from oocytes following application of glutamate revealed a strong reduction in glutamate uptake currents (46.3 +/- 10.2%) as compared to controls, Finally, clozapine treatment led to increases in both the mean basal (8.1 +/- 0.7 muM) and the KCl-evoked (28.7 +/- 7.7 muM) output of glutamate that were 3.1 and 3.5, respectively, higher than in control rats. These findings indicate that clozapine may potentiate glutamatergic synaptic transmission by regulating glutamate transport.

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Documento generato il 20/01/20 alle ore 10:41:19