Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia
Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia
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DOI：
10.1016/j.biopsych.2006.12.005
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发表时间：
2007-10-01
影响因子：
10.6
通讯作者：
Ferraguti, Francesco
中科院分区：
文献类型：
--
作者：
Corti, Corrado;Crepaldi, Luca;Ferraguti, Francesco
背景：代谢型谷氨酸受体（mGlus）可能参与精神分裂症的病理生理过程。II组mGlus自从开发出表现出非典型抗精神病样活性的有效特异性激动剂以及mGlu 3基因与精神分裂症之间的遗传关联的报道以来，mGlu 2和mGlu 3基因引起了相当大的兴趣。在这个死后研究中，精神分裂症患者（n = 20）和对照组（n = 35）前额叶Brodmann 10区mGlu 3蛋白水平使用新型特异性mGlu 3抗体和囊泡谷氨酸转运蛋白1（VGluT 1）抗体通过蛋白质免疫印迹分析受试者。我们报告了与对照组相比，精神分裂症患者中mGlu 3的二聚体/寡聚体形式显著减少，而总mGlu 3和VGluT 1水平没有显着改变Conclusions：这是第一个实验证据表明，mGlu 3受体水平改变精神分裂症，并支持这一假设，涉及这种特殊的兴奋性氨基酸受体的神经传递受损精神分裂症。
Background: Metabotropic glutamate receptors (mGlus) maybe 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.