精神分裂症中代谢型谷氨酸受体3的二聚化改变
Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia.
作者信息
Corti Corrado, Crepaldi Luca, Mion Silvia, Roth Adelheid L, Xuereb John H, Ferraguti Francesco
机构信息
Department of Biology, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline Medicines Research Centre, Verona, Italy.
出版信息
Biol Psychiatry. 2007 Oct 1;62(7):747-55. doi: 10.1016/j.biopsych.2006.12.005. Epub 2007 May 24.
BACKGROUND
Metabotropic glutamate receptors (mGlus) may be involved in the pathophysiology of schizophrenia. Group II mGlus (mGlu2 and mGlu3) have attracted considerable interest since the development of potent specific agonists that exhibit atypical antipsychotic-like activity and reports of a genetic association between the mGlu3 gene and schizophrenia.
METHODS
In this postmortem study, mGlu3 protein levels in Brodmann area 10 of prefrontal cortex from schizophrenic (n = 20) and control (n = 35) subjects were analyzed by western immunoblotting using a novel specific mGlu3 antibody and an antibody for the vesicular glutamate transporter 1 (VGluT1).
RESULTS
We report a significant decrease in the dimeric/oligomeric forms of mGlu3 in schizophrenic patients compared with control subjects, whereas total mGlu3 and VGluT1 levels were not altered significantly.
CONCLUSIONS
This is the first experimental evidence that mGlu3 receptor levels are altered in schizophrenia and supports the hypothesis that neurotransmission involving this particular excitatory amino acid receptor is impaired in schizophrenia.
背景
代谢型谷氨酸受体（mGlu）可能参与精神分裂症的病理生理学过程。自强效特异性激动剂出现以来，II 型 mGlu（mGlu2 和 mGlu3）引起了广泛关注，这些激动剂表现出非典型抗精神病样活性，并且有报道称 mGlu3 基因与精神分裂症之间存在遗传关联。
方法
在这项尸检研究中，使用一种新型特异性 mGlu3 抗体和囊泡谷氨酸转运体 1（VGluT1）抗体，通过蛋白质免疫印迹法分析了精神分裂症患者（n = 20）和对照受试者（n = 35）前额叶皮质 Brodmann 区 10 中的 mGlu3 蛋白水平。
结果
我们发现，与对照受试者相比，精神分裂症患者中 mGlu3 的二聚体/寡聚体形式显著减少，而 mGlu3 和 VGluT1 的总水平没有明显改变。
结论
这是首个表明精神分裂症中 mGlu3 受体水平发生改变的实验证据，支持了精神分裂症中涉及这种特定兴奋性氨基酸受体的神经传递受损的假说。
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