Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both Fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism.
Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both Fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism.
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DOI：
10.1002/ar.21299
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发表时间：
2011-10
影响因子：
2
通讯作者：
Liesch, Stephanie B.
中科院分区：
文献类型：
--
作者：
Fatemi, S. Hossein;Folsom, Timothy D.;Kneeland, Rachel E.;Liesch, Stephanie B.
最近的研究已经证明了脑gaba能信号系统功能障碍的影响以及由此导致的自闭症患者的行为病理。在动物模型中，脆性X智力迟钝蛋白（FMRP）的表达改变与GABA受体的下调有关。有趣的是，在患有脆性X综合征的个体中也观察到自闭症表型。本研究旨在验证先前有关FMRP水平异常与GABAA受体低表达的理论。我们观察到自闭症成人蚓部的FMRP水平显著降低。此外，我们发现，与年龄和死后间隔（PMI）匹配的对照组相比，自闭症儿童蚓部的代谢性谷氨酸受体5 （mGluR5）蛋白水平显著升高。成人自闭症患者蚓部GABAA受体β3 （GABRβ3）蛋白水平也显著降低。最后，我们发现，与对照组相比，儿童和成人自闭症患者蚓部的胶质纤维酸性蛋白（GFAP）显著增加。综上所述，我们的研究结果进一步证明，FMRP表达的改变和mGluR5蛋白产生的增加可能导致GABAA受体表达的改变。
Recent work has demonstrated the impact of dysfunction of the GABAergic signaling system in brain and the resultant behavioral pathologies in subjects with autism. In animal models, altered expression of Fragile X mental retardation protein (FMRP) has been linked to downregulation of GABA receptors. Interestingly, the autistic phenotype is also observed in individuals with Fragile X syndrome. This study was undertaken to test previous theories relating abnormalities in levels of FMRP to GABAA receptor underexpression. We observed a significant reduction in levels of FMRP in the vermis of adults with autism. Additionally, we found that levels of metabotropic glutamate receptor 5 (mGluR5) protein were significantly increased in vermis of children with autism vs. age and postmortem interval (PMI) matched controls. There was also a significant decrease in level of GABAA receptor beta 3 (GABRβ3) protein in vermis of adult subjects with autism. Finally, we found significant increases in glial fibrillary acidic protein (GFAP) in vermis of both children and adults with autism when compared with controls. Taken together, our results provide further evidence that altered FMRP expression and increased mGluR5 protein production potentially leads to altered expression of GABAA receptors.
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