Downregulation of GABAA receptor protein subunits α6, β2, δ, ε, γ2, θ, and ρ2 in superior frontal cortex of subjects with autism

S H Fatemi; Teri J. Reutiman; Timothy D. Folsom; Oyvind G. Rustan; Robert J. Rooney; Paul D. Thuras

doi:10.1007/s10803-014-2078-x

Downregulation of GABA_A receptor protein subunits α6, β2, δ, ε, γ2, θ, and ρ2 in superior frontal cortex of subjects with autism

S H Fatemi, Teri J. Reutiman, Timothy D. Folsom, Oyvind G. Rustan, Robert J. Rooney, Paul D. Thuras

Psychiatry & Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

Abstract

We measured protein and mRNA levels for nine gamma-aminobutyric acid A (GABA_A) 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 GABA_A and GABA_B subunits and overall reduced protein expression for GABA_A receptor alpha 6 (GABRα6), GABA_A receptor beta 2 (GABRβ2), GABA_A receptor delta (GABRδ), GABA _A receptor epsilon (GABRε), GABA_A receptor gamma 2 (GABRγ2), GABA_A receptor theta (GABRθ), and GABA _A receptor rho 2 (GABRρ2) in superior frontal cortex from subjects with autism. Our data demonstrate systematic changes in GABA _A&B subunit expression in brains of subjects with autism, which may help explain the presence of cognitive abnormalities in subjects with autism.

Original language	English (US)
Pages (from-to)	1833-1845
Number of pages	13
Journal	Journal of Autism and Developmental Disorders
Volume	44
Issue number	8
DOIs	https://doi.org/10.1007/s10803-014-2078-x
State	Published - Aug 2014

Bibliographical note

Funding Information:
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.

Keywords

Autism
Brain
Frontal cortex
GABA
GABRα6
GABRβ2

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title = "Downregulation of GABAA receptor protein subunits α6, β2, δ, ε, γ2, θ, and ρ2 in superior frontal cortex of subjects with autism",

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), GABA A receptor epsilon (GABRε), GABAA receptor gamma 2 (GABRγ2), GABAA receptor theta (GABRθ), and GABA A receptor rho 2 (GABRρ2) in superior frontal cortex from subjects with autism. Our data demonstrate systematic changes in GABA A&B subunit expression in brains of subjects with autism, which may help explain the presence of cognitive abnormalities in subjects with autism.",

keywords = "Autism, Brain, Frontal cortex, GABA, GABRα6, GABRβ2",

author = "Fatemi, {S H} and Reutiman, {Teri J.} and Folsom, {Timothy D.} and Rustan, {Oyvind G.} and Rooney, {Robert J.} and Thuras, {Paul D.}",

note = "Funding Information: 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.",

year = "2014",

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doi = "10.1007/s10803-014-2078-x",

language = "English (US)",

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AU - Fatemi, S H

AU - Reutiman, Teri J.

AU - Folsom, Timothy D.

AU - Rustan, Oyvind G.

AU - Rooney, Robert J.

AU - Thuras, Paul D.

N1 - Funding Information: 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.

PY - 2014/8

Y1 - 2014/8

N2 - 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), GABA A receptor epsilon (GABRε), GABAA receptor gamma 2 (GABRγ2), GABAA receptor theta (GABRθ), and GABA A receptor rho 2 (GABRρ2) in superior frontal cortex from subjects with autism. Our data demonstrate systematic changes in GABA A&B subunit expression in brains of subjects with autism, which may help explain the presence of cognitive abnormalities in subjects with autism.

AB - 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), GABA A receptor epsilon (GABRε), GABAA receptor gamma 2 (GABRγ2), GABAA receptor theta (GABRθ), and GABA A receptor rho 2 (GABRρ2) in superior frontal cortex from subjects with autism. Our data demonstrate systematic changes in GABA A&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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KW - GABRβ2

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