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Titolo:
Biological research on schizophrenia
Autore:
Toru, M;
Indirizzi:
Tokyoapan & Dent Univ, Sch Med, Dept Neuropsychiat, Bunkyo Ku, Tokyo 113, J Tokyo Med & Dent Univ Tokyo Japan 113 opsychiat, Bunkyo Ku, Tokyo 113, J
Titolo Testata:
PSYCHIATRY AND CLINICAL NEUROSCIENCES
, volume: 52, anno: 1998, supplemento:, S
pagine: S170 - S172
SICI:
1323-1316(199812)52:<S170:BROS>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOPAMINE D2 RECEPTOR; BINDING-SITES; CEREBROSPINAL-FLUID; ACID BINDING; BRAIN; PHENCYCLIDINE; GLUTAMATE; POSTMORTEM; HYPOTHESIS; CORTEX;
Keywords:
dopamine D2 receptor; dopamine D2 receptor gene; glutamate receptors; kainate receptor; N-methyl-D-aspartate receptor; schizophrenia; tyrosine hydroxylase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Toru, M Tokyoma,d & Dent Univ, Sch Med, Dept Neuropsychiat, Bunkyo Ku, 1-5-45 Yushi Tokyo Med & Dent Univ 1-5-45 Yushima Tokyo Japan 113 1-5-45 Yushi
Citazione:
M. Toru, "Biological research on schizophrenia", PSY CLIN N, 52, 1998, pp. S170-S172

Abstract

Based on the biochemical analysis of postmortem brains from chronic schizophrenic patients, we found abnormalities of glutamatergic neurons as well as dopaminergic neurons. Glutamate receptors, such as the kainate receptor labeled by H-3-kainate, the N-methyl-D-asparatate (NMDA) receptor by H-3 MK801, and the styrchnine-insensitive glycine sites in the NMDA receptor by H-3-glycine, increased significantly in various cortical areas of schizophrenic brains. According tp the animal experiments and a significant negative correlation between kainate binding values and glutamate concentrations, it is suggested that glutamate receptors increased due to hypoglutamatergic function in the brain of chronic schizophrenia. Hyperdopamine hippothesis of schizophrenia is supported by the correlation between affinity to dopamine receptor and clinical potency of antipyschotic drugs. Measurement of tyrosine hydroxylase activity and dopamine D2 receptor in the schizophrenic brainprovided evidence of hyperdominergia. Association study of a missense variant in the dopamine D2 receptor gene (Cys 311) revealed that the allele frequency of the variant was significantly higher int he schizophrenic patients than the controls. The patients carrying this variant had less severe negative symptoms and better response to antipsychotic drug treatment. Dopamine-induced sequestration of dopamine D2S receptor with Cys variant expressedin CHO cells was shown to a lesser extent than wild-type receptor. This experimental results may be consistent with better responsiveness of the patients with Cys311 to antipsychotic drugs.

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Documento generato il 04/07/20 alle ore 14:07:49