title: mRNA and protein expression for novel GABAA 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 (GABAA) receptor mRNAs. Previous work by our laboratory has found reduced expression of FMRP, as well as multiple GABAA and GABAB receptor subunits in subjects with autism. Less is known about levels for GABAA 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 GABAA 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.
authors.affiliation: Division of Neuroscience Research, Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA. fatem002@umn.edu
authors.forename: S H
authors.initials: SH
authors.lastname: Fatemi
authors.forename: T D
authors.initials: TD
authors.lastname: Folsom
authors.forename: R J
authors.initials: RJ
authors.lastname: Rooney
authors.forename: P D
authors.initials: PD
authors.lastname: Thuras
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics* / Q000502:physiology; D011963:Receptors, GABA-A / Q000235:genetics* / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D011963:Receptors, GABA-A; C497683:FMR1 protein, human; C578935:GRM5 protein, human