Expression of excitatory amino acid transporter transcripts in the thalamus of subjects with schizophrenia
Expression of excitatory amino acid transporter transcripts in the thalamus of subjects with schizophrenia
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DOI：
10.1176/appi.ajp.158.9.1393
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发表时间：
2001-09-01
影响因子：
17.7
通讯作者：
Meador-Woodruff, JH
中科院分区：
文献类型：
--
作者：
Smith, RE;Haroutunian, V;Meador-Woodruff, JH
目的：近年来，精神分裂症的研究主要集中在多巴胺能神经传递，因为苯环利定是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，可诱导精神分裂症样症状。精神病作者先前报道了精神分裂症患者丘脑NMDA受体亚单位表达的改变，这与丘脑NMDA能功能减退可能导致这种疾病的病理生理学的假设一致。在这项研究中，他们将这一假设推广到包括谷氨酸突触的其他分子，特别是兴奋性氨基酸转运蛋白（EAAT），其在丘脑中的正常表达和调节也可能在精神分裂症患者中被破坏。方法：用对人兴奋性氨基酸转运蛋白转录本EAAT 1，EAAT 2，结果：在精神分裂症患者的丘脑核团中检测到EAAT 1和EAAT 2的高表达，而EAAT 3则无表达。这些发现支持了精神分裂症中谷氨酸能功能障碍的假设，并表明谷氨酸受体以外的分子在这种疾病中的谷氨酸能突触中异常表达。
Objective: Recent investigations of schizophrenia have targeted glutamatergic neurotransmission, since phencyclidine, an N-methyl-D-aspartate (NMDA) receptor antagonist, can induce schizophreniform. psychosis. The authors previously reported alterations in thalamic NMDA receptor subunit expression in schizophrenia, consistent with the hypothesis that thalamic glutamatergic hypofunction may contribute to the pathophysiology of this illness. In this study they generalized this hypothesis to include other molecules of the glutamate synapse, specifically excitatory amino acid transporters (EAATs), whose normal expression and regulation in the thalamus may also be disrupted in subjects with schizophrenia.Method: in situ hybridization with riboprobes specific for the human excitatory amino acid transporter transcripts EAAT1, EAAT2, and EAAT3 was performed in discrete thalamic nuclei in persons with schizophrenia and comparison subjects.Results: Higher expressions of transcripts encoding EAAT1 and EAAT2, but not EAAT3, were detected in the thalamus of subjects with schizophrenia.Conclusions: These findings support the hypothesis of glutamatergic dysfunction in schizophrenia and suggest that molecules other than glutamate receptors are abnormally expressed in glutamatergic synapses in this illness.