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Downregulation of GABAA Receptor Protein Subunits α6, β2, δ, ε, γ2, θ, and ρ2 in Superior Frontal Cortex of Subjects with Autism

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Abstract

We measured protein and mRNA levels for nine gamma-aminobutyric acid A (GABAA) receptor subunits in three brain regions (cerebellum, superior frontal cortex, and parietal cortex) in subjects with autism versus matched controls. We observed changes in mRNA for a number of GABAA and GABAB subunits and overall reduced protein expression for GABAA receptor alpha 6 (GABRα6), GABAA receptor beta 2 (GABRβ2), GABAA receptor delta (GABRδ), GABAA receptor epsilon (GABRε), GABAA receptor gamma 2 (GABRγ2), GABAA receptor theta (GABRθ), and GABAA receptor rho 2 (GABRρ2) in superior frontal cortex from subjects with autism. Our data demonstrate systematic changes in GABAA&B subunit expression in brains of subjects with autism, which may help explain the presence of cognitive abnormalities in subjects with autism.

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Acknowledgments

Human tissue was obtained from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) Brain and Tissue Bank for Developmental Disorders, University of Maryland, Baltimore, MD (The role of the NICHD Brain and Tissue Bank is to distribute tissue, and therefore, cannot endorse the studies performed or the interpretation of results); the Harvard Brain Tissue Resource Center, which is supported in part by Public Health Service 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 the Eunice Kennedy Shriver National Institute of Child Health and Human Development (#5R01HD052074-01A2 and 3R01HD052074-03S1) and the Minnesota Medical Foundation Alfred and Ingrid Lenz Harrison Autism Initiative Fund to SHF is gratefully acknowledged. Dr. Fatemi is currently supported by the Bernstein Endowed Professorship in Adult Psychiatry.

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The authors declare that there is no conflict of interest.

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Author notes

  1. Teri J. Reutiman

    Present address: Regions Hospital, 640 Jackson St., St. Paul, MN, 55101, USA

  2. Oyvind G. Rustan

    Present address: Oslo University Hospital, Kirkeveien 166, 0450, Oslo, Norway

Authors and Affiliations

  1. Division of Neuroscience Research, Department of Psychiatry, University of Minnesota Medical School, 420 Delaware St SE, MMC 392, Minneapolis, MN, 55455, USA

    S. Hossein Fatemi & Timothy D. Folsom

  2. Department of Pharmacology, University of Minnesota Medical School, 310 Church St. SE, Minneapolis, MN, 55455, USA

    S. Hossein Fatemi

  3. Department of Neuroscience, University of Minnesota Medical School, 321 Church St. SE, Minneapolis, MN, 55455, USA

    S. Hossein Fatemi

  4. Genome Explorations, 654 Jefferson Avenue, Memphis, TN, 84322, USA

    Robert J. Rooney

  5. Department of Psychiatry (116A), Minneapolis Veterans Administration Medical Center, 1 Veterans Drive, Minneapolis, MN, 55417, USA

    Paul D. Thuras

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  1. S. Hossein Fatemi
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Correspondence to S. Hossein Fatemi.

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Fatemi, S.H., Reutiman, T.J., Folsom, T.D. et al. Downregulation of GABAA Receptor Protein Subunits α6, β2, δ, ε, γ2, θ, and ρ2 in Superior Frontal Cortex of Subjects with Autism. J Autism Dev Disord 44, 1833–1845 (2014). https://doi.org/10.1007/s10803-014-2078-x

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