A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction
A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction
复制标题
DOI：
10.1016/s0091-3057(96)00428-5
复制
发表时间：
1997-04-01
影响因子：
3.6
通讯作者：
deBelleroche, J
中科院分区：
文献类型：
--
作者：
Hirsch, SR;Das, I;deBelleroche, J
越来越多的证据表明精神分裂症存在谷氨酸功能障碍，精神分裂症和苯环己哌啶精神病相似，并且已知苯环己哌啶可以阻断谷氨酸的 N-甲基-D-天冬氨酸 (NMDA) 亚型，这一事实表明了这一点。两者都主要发生在青春期之后，表明它们可能具有相似的潜在发育过程。现在，从信使 RNA 的研究中积累的直接证据表明，谷氨酸受体缺陷发生在精神分裂症中，并且具有区域性和特异性分布。这些结果得到了对哺乳动物和人类的记忆、电生理学发现、临床治疗和药理学研究的支持。我们最近的发现：a）额叶和颞叶皮层第 III 层锥体细胞树突棘显着减少，b）NMDA 谷氨酸受体 mRNA 减少与老年精神分裂症患者认知恶化之间的相关性大于 0.90，这是迄今为止最有力的证据，表明谷氨酸功能障碍在精神分裂症中发挥着重要作用。 (C) 1997 爱思唯尔科学公司。
There is mounting evidence of a glutamate dysfunction in schizophrenia, as suggested by the fact that schizophrenia and phencyclidine psychosis are similar and phencyclidine is known to block the N-methyl-D-aspartate (NMDA) subtypes of glutamate. Both occur mainly after puberty, suggesting they may share similar underlying developmental processes. Direct evidence is now accumulating from the study of messenger RNA that glutamate receptor deficiencies occur in schizophrenia and are regionally and specifically distributed. These results find support from studies of memory, electrophysiological findings, clinical treatment, and pharmacological studies in mammals and humans. Our recent findings of: a) a marked decrease in pyramidal cell dendritic spines in layer III of the frontal and temporal cortex, and b) a greater than 0.90 correlation between decrease in mRNA for the NMDA glutamate receptor and cognitive deterioration in elderly schizophrenics, present the strongest evidence to date that glutamate dysfunction plays an important role in schizophrenia. (C) 1997 Elsevier Science Inc.