Abstract
Gamma-aminobutyric acid A (GABAA) receptors are ligand-gated ion channels responsible for mediation of fast inhibitory action of GABA in the brain. Preliminary reports have demonstrated altered expression of GABA receptors in the brains of subjects with autism suggesting GABA/glutamate system dysregulation. We investigated the expression of four GABAA receptor subunits and observed significant reductions in GABRA1, GABRA2, GABRA3, and GABRB3 in parietal cortex (Brodmann’s Area 40 (BA40)), while GABRA1 and GABRB3 were significantly altered in cerebellum, and GABRA1 was significantly altered in superior frontal cortex (BA9). The presence of seizure disorder did not have a significant impact on GABAA receptor subunit expression in the three brain areas. Our results demonstrate that GABAA receptors are reduced in three brain regions that have previously been implicated in the pathogenesis of autism, suggesting widespread GABAergic dysfunction in the brains of subjects with autism.
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Acknowledgments
Human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders; the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number R24 MH068855; the Brain Endowment Bank, which is funded in part by the National Parkinson Foundation, Inc., Miami, Florida; and the Autism Tissue Program and is gratefully acknowledged. Grant support by Eunice Kennedy Shriver National Institute of Child Health and Human Development (#5R01HD052074-01A2) to SHF is gratefully acknowledged.
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Fatemi, S.H., Reutiman, T.J., Folsom, T.D. et al. GABAA Receptor Downregulation in Brains of Subjects with Autism. J Autism Dev Disord 39, 223–230 (2009). https://doi.org/10.1007/s10803-008-0646-7
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DOI: https://doi.org/10.1007/s10803-008-0646-7