MRNA and protein expression for novel GABA A receptors θ and ρ2 are altered in schizophrenia and mood disorders; Relevance to FMRP-mGluR5 signaling pathway

S. H. Fatemi, T. D. Folsom, Robert Rooney, P. D. Thuras

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Fragile X mental retardation protein (FMRP) is an RNA-binding protein that targets ∼5% of all mRNAs expressed in the brain. Previous work by our laboratory demonstrated significantly lower protein levels for FMRP in lateral cerebella of subjects with schizophrenia, bipolar disorder and major depression when compared with controls. Absence of FMRP expression in animal models of fragile X syndrome (FXS) has been shown to reduce expression of gamma-aminobutyric acid A (GABA A) receptor mRNAs. Previous work by our laboratory has found reduced expression of FMRP, as well as multiple GABA A and GABA B receptor subunits in subjects with autism. Less is known about levels for GABA A subunit protein expression in brains of subjects with schizophrenia and mood disorders. In the current study, we have expanded our previous studies to examine the protein and mRNA expression of two novel GABA A receptors, theta (GABRθ) and rho 2 (GABRρ2) as well as FMRP, and metabotropic glutamate receptor 5 (mGluR5) in lateral cerebella of subjects with schizophrenia, bipolar disorder, major depression and healthy controls, and in superior frontal cortex (Brodmann Area 9 (BA9)) of subjects with schizophrenia, bipolar disorder and healthy controls. We observed multiple statistically significant mRNA and protein changes in levels of GABRθ, GABRρ2, mGluR5 and FMRP molecules including concordant reductions in mRNA and proteins for GABRθ and mGluR5 in lateral cerebella of subjects with schizophrenia; for increased mRNA and protein for GABRρ2 in lateral cerebella of subjects with bipolar disorder; and for reduced mRNA and protein for mGluR5 in BA9 of subjects with bipolar disorder. There were no significant effects of confounds on any of the results.

Original languageEnglish (US)
Article numbere271
JournalTranslational Psychiatry
Volume3
DOIs
StatePublished - Jul 15 2013
Externally publishedYes

Fingerprint

Fragile X Mental Retardation Protein
Metabotropic Glutamate 5 Receptor
GABA Receptors
Mood Disorders
Schizophrenia
Bipolar Disorder
Messenger RNA
Cerebellum
Proteins
gamma-Aminobutyric Acid
Depression
GABA-B Receptors
Fragile X Syndrome
RNA-Binding Proteins
Protein Subunits
Brain
Frontal Lobe
Autistic Disorder
Animal Models

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

@article{72f7e049c22f4e2fb5030e99ce3e7c5f,
title = "MRNA and protein expression for novel GABA A receptors θ and ρ2 are altered in schizophrenia and mood disorders; Relevance to FMRP-mGluR5 signaling pathway",
abstract = "Fragile X mental retardation protein (FMRP) is an RNA-binding protein that targets ∼5{\%} of all mRNAs expressed in the brain. Previous work by our laboratory demonstrated significantly lower protein levels for FMRP in lateral cerebella of subjects with schizophrenia, bipolar disorder and major depression when compared with controls. Absence of FMRP expression in animal models of fragile X syndrome (FXS) has been shown to reduce expression of gamma-aminobutyric acid A (GABA A) receptor mRNAs. Previous work by our laboratory has found reduced expression of FMRP, as well as multiple GABA A and GABA B receptor subunits in subjects with autism. Less is known about levels for GABA A subunit protein expression in brains of subjects with schizophrenia and mood disorders. In the current study, we have expanded our previous studies to examine the protein and mRNA expression of two novel GABA A receptors, theta (GABRθ) and rho 2 (GABRρ2) as well as FMRP, and metabotropic glutamate receptor 5 (mGluR5) in lateral cerebella of subjects with schizophrenia, bipolar disorder, major depression and healthy controls, and in superior frontal cortex (Brodmann Area 9 (BA9)) of subjects with schizophrenia, bipolar disorder and healthy controls. We observed multiple statistically significant mRNA and protein changes in levels of GABRθ, GABRρ2, mGluR5 and FMRP molecules including concordant reductions in mRNA and proteins for GABRθ and mGluR5 in lateral cerebella of subjects with schizophrenia; for increased mRNA and protein for GABRρ2 in lateral cerebella of subjects with bipolar disorder; and for reduced mRNA and protein for mGluR5 in BA9 of subjects with bipolar disorder. There were no significant effects of confounds on any of the results.",
author = "Fatemi, {S. H.} and Folsom, {T. D.} and Robert Rooney and Thuras, {P. D.}",
year = "2013",
month = "7",
day = "15",
doi = "10.1038/tp.2013.46",
language = "English (US)",
volume = "3",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - MRNA and protein expression for novel GABA A receptors θ and ρ2 are altered in schizophrenia and mood disorders; Relevance to FMRP-mGluR5 signaling pathway

AU - Fatemi, S. H.

AU - Folsom, T. D.

AU - Rooney, Robert

AU - Thuras, P. D.

PY - 2013/7/15

Y1 - 2013/7/15

N2 - Fragile X mental retardation protein (FMRP) is an RNA-binding protein that targets ∼5% of all mRNAs expressed in the brain. Previous work by our laboratory demonstrated significantly lower protein levels for FMRP in lateral cerebella of subjects with schizophrenia, bipolar disorder and major depression when compared with controls. Absence of FMRP expression in animal models of fragile X syndrome (FXS) has been shown to reduce expression of gamma-aminobutyric acid A (GABA A) receptor mRNAs. Previous work by our laboratory has found reduced expression of FMRP, as well as multiple GABA A and GABA B receptor subunits in subjects with autism. Less is known about levels for GABA A subunit protein expression in brains of subjects with schizophrenia and mood disorders. In the current study, we have expanded our previous studies to examine the protein and mRNA expression of two novel GABA A receptors, theta (GABRθ) and rho 2 (GABRρ2) as well as FMRP, and metabotropic glutamate receptor 5 (mGluR5) in lateral cerebella of subjects with schizophrenia, bipolar disorder, major depression and healthy controls, and in superior frontal cortex (Brodmann Area 9 (BA9)) of subjects with schizophrenia, bipolar disorder and healthy controls. We observed multiple statistically significant mRNA and protein changes in levels of GABRθ, GABRρ2, mGluR5 and FMRP molecules including concordant reductions in mRNA and proteins for GABRθ and mGluR5 in lateral cerebella of subjects with schizophrenia; for increased mRNA and protein for GABRρ2 in lateral cerebella of subjects with bipolar disorder; and for reduced mRNA and protein for mGluR5 in BA9 of subjects with bipolar disorder. There were no significant effects of confounds on any of the results.

AB - Fragile X mental retardation protein (FMRP) is an RNA-binding protein that targets ∼5% of all mRNAs expressed in the brain. Previous work by our laboratory demonstrated significantly lower protein levels for FMRP in lateral cerebella of subjects with schizophrenia, bipolar disorder and major depression when compared with controls. Absence of FMRP expression in animal models of fragile X syndrome (FXS) has been shown to reduce expression of gamma-aminobutyric acid A (GABA A) receptor mRNAs. Previous work by our laboratory has found reduced expression of FMRP, as well as multiple GABA A and GABA B receptor subunits in subjects with autism. Less is known about levels for GABA A subunit protein expression in brains of subjects with schizophrenia and mood disorders. In the current study, we have expanded our previous studies to examine the protein and mRNA expression of two novel GABA A receptors, theta (GABRθ) and rho 2 (GABRρ2) as well as FMRP, and metabotropic glutamate receptor 5 (mGluR5) in lateral cerebella of subjects with schizophrenia, bipolar disorder, major depression and healthy controls, and in superior frontal cortex (Brodmann Area 9 (BA9)) of subjects with schizophrenia, bipolar disorder and healthy controls. We observed multiple statistically significant mRNA and protein changes in levels of GABRθ, GABRρ2, mGluR5 and FMRP molecules including concordant reductions in mRNA and proteins for GABRθ and mGluR5 in lateral cerebella of subjects with schizophrenia; for increased mRNA and protein for GABRρ2 in lateral cerebella of subjects with bipolar disorder; and for reduced mRNA and protein for mGluR5 in BA9 of subjects with bipolar disorder. There were no significant effects of confounds on any of the results.

UR - http://www.scopus.com/inward/record.url?scp=84879977184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879977184&partnerID=8YFLogxK

U2 - 10.1038/tp.2013.46

DO - 10.1038/tp.2013.46

M3 - Article

VL - 3

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

M1 - e271

ER -