Altered mRNA Levels of Glucocorticoid Receptor, Mineralocorticoid Receptor, and Co-Chaperones (FKBP5 and PTGES3) in the Middle Frontal Gyrus of Autism Spectrum Disorder Subjects.
Although stress has been implicated in the pathophysiology of autistic spectrum disorder (ASD), it is not known whether glucocorticoid receptor (GR) levels are altered in the brain of subjects with ASD. The messenger RNA (mRNA) levels of GR isoforms (GRα, GRβ, GRγ, and GRP), mineralocorticoid receptor (MR), GR co-chaperones (FKBP5, PTGES3, and BAG1), and inflammatory cytokines (IL-6, IL-1β, and IFN-γ) were examined in the postmortem middle frontal gyrus tissues of 13 ASD and 13 age-matched controls by qRT-PCR. The protein levels were examined by Western blotting. We found significant decreases in GRα (64%), GRγ (48%), GRP (20%) and MR (46%) mRNA levels in ASD subjects as compared to controls. However, significant increases in FKBP5 (42%) and PTGES3 (35%) mRNA levels were observed in ASD subjects. There were no differences in the mRNA levels of GRβ and BAG1 in ASD subjects as compared to controls. MR mRNA was found to be negatively correlated with the diagnostic score for abnormality of development. On the protein level, significant reductions in GR and MR, but no change in FKBP5 and PTGES3 were found in ASD subjects as compared to controls. Moreover, we observed significant increases in IL-1β and IFN-γ mRNA levels in ASD subjects, and these cytokines were negatively associated with GR levels. Our data, for the first time, reports dysregulation of GR, MR, FKBP5, and PTGES3 in ASD and suggest a possible role of inflammation in altered GR function in ASD.
Department of Psychiatry and Health Behavior, Medical College of Georgia, Georgia Regents University, 997 St. Sebastian Way, Augusta, GA, 30912, USA.
Neil
N
Patel
Department of Psychiatry and Health Behavior, Medical College of Georgia, Georgia Regents University, 997 St. Sebastian Way, Augusta, GA, 30912, USA.
Amanda
A
Crider
Department of Psychiatry and Health Behavior, Medical College of Georgia, Georgia Regents University, 997 St. Sebastian Way, Augusta, GA, 30912, USA.
Chirayu D
CD
Pandya
Department of Psychiatry, Weill Cornell Medical College, 21 Bloomingdale Rd, White Plains, NY, 10605, USA.
Anthony O
AO
Ahmed
Department of Psychiatry and Health Behavior, Medical College of Georgia, Georgia Regents University, 997 St. Sebastian Way, Augusta, GA, 30912, USA. apillai@gru.edu.
Anilkumar
A
Pillai
D000067877:Autism Spectrum Disorder / Q000235:genetics*; D002648:Child; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology*; D000071876:Prostaglandin-E Synthases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism; D018709:Statistics, Nonparametric; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
D007371:Interferon-gamma; D053583:Interleukin-1beta; D018832:Molecular Chaperones; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C490849:PTGES3 protein, human
Autism; Brain; Glucocorticoid; Mineralocorticoid; Receptor; Stress