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

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 GABA(A) 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 versus age and postmortem interval matched controls. There was also a significant decrease in level of GABA(A) receptor beta 3 (GABR beta 3) protein in vermis of adult subjects with autism. Finally, we found significant increases in glial fibrillary acidic protein 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 lead to altered expression of GABA(A) receptors. Anat Rec, 294: 1635-1645, 2011. (C) 2011 Wiley-Liss, Inc.