GABAergic mechanisms of hippocampal hyperactivity in schizophrenia.

GABAergic mechanisms of hippocampal hyperactivity in schizophrenia.
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DOI:
10.1016/j.schres.2014.09.041
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发表时间:
2015-09
影响因子:
4.5
通讯作者:
Konradi, Christine
Konradi, Christine
中科院分区:
医学2区
文献类型:
--
作者:
Heckers, Stephan;Konradi, Christine

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精神分裂症与海马结构和功能异常有关。神经影像学研究表明,精神分裂症患者的海马体过度活跃。在这里,我们探讨这种海马活动过度的GABA能机制。精神分裂症患者海马GABA能异常的最初证据来自于对中间神经元数量、蛋白表达和基因表达的死后研究。这些研究表明,生长抑素阳性和小清蛋白阳性的中间神经元的基因和蛋白表达显着下降,并表示减少中间神经元的数量。对小清蛋白和NMDA受体功能降低的动物研究表明,海马中间神经元的选择性异常模拟了精神分裂症的一些认知缺陷和临床特征。尸检和动物研究与精神分裂症海马活动增加的神经影像学发现一致,这可以解释一些精神病症状和认知缺陷。总之,这些发现可能会指导生物标志物的开发和精神病新疗法的开发。
Schizophrenia is associated with abnormalities of hippocampal structure and function. Neuroimaging studies have shown that the hippocampus is hyperactive in schizophrenia. Here we explore GABAergic mechanisms of this hippocampal hyperactivity. The initial evidence for GABAergic abnormalities of the hippocampus in schizophrenia came from post-mortem studies of interneuron number, protein expression, and gene expression. These studies revealed marked decreases in gene and protein expression of somatostatin-positive and parvalbumin-positive interneurons, and indicated reduced interneuron numbers. Animal studies of decreased parvalbumin and NMDA-receptor function have shown that selective abnormalities of hippocampal interneurons mimic some of the cognitive deficits and clinical features of schizophrenia. The post-mortem and animal studies are consistent with the neuroimaging finding of increased hippocampal activity in schizophrenia, which can explain some of the psychotic symptoms and cognitive deficits. Taken together, these findings may guide the development of biomarkers and the development of new treatments for psychosis.
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