GABAA Receptor Downregulation in Brains of Subjects with Autism
Open accessAbstract
Gamma-aminobutyric acid A (GABA(A)) 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 GABA(A) 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 GABA(A) receptor subunit expression in the three brain areas. Our results demonstrate that GABA(A) 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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GABAergic dysfunction in the cerebellum in autism has been demonstrated repeatedly.
“GABAergic dysfunction in the cerebellum in autism has been demonstrated repeatedly [70, 124, 261].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [70]
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- Authors
- Fatemi, S. H., Reutiman, T. J., Folsom, T. D., & Thuras, P. D.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Fatemi, S. Hossein
- Venue
- Journal of Autism and Developmental Disorders
- Published
- 2008-09-23
- Volume
- 39
- Issue
- 2
- Pages
- 223-230
- ISSN
- 0162-3257 (ISSN-L)
- 1573-3432
- PMC
- PMC2697059
- OpenAlex
- W2035027696
- Cited by
- 439
- References
- 52
- Citations by year
- 2026: 15 · 2025: 11 · 2024: 14 · 2023: 24 · 2022: 26 · 2021: 26 · 2020: 26 · 2019: 27 · 2018: 21 · 2017: 30 · 2016: 26 · 2015: 30 · 2014: 37 · 2013: 35 · 2012: 29
- FWCI
- 10.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Autism and Developmental Disorders (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Parkinson Foundation
- National Institutes of Health
- National Institute of Mental Health (R24MH068855)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD052074)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- GABAA receptor, receptor subunit expression, autism spectrum disorder, GABRA1, GABRA2, GABRA3, GABRB3, GABAergic dysfunction, parietal cortex, cerebellum, superior frontal cortex, epilepsy
- MeSH terms
- Adult, Autistic Disorder, Brain, Cerebellum, Electrophoresis, Polyacrylamide Gel, Epilepsy, Female, Frontal Lobe, Humans, Male, Middle Aged, Parietal Lobe, Postmortem Changes, Receptors, GABA-A, Blotting, Western, Down-Regulation, Young Adult
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