Authors: Neil Patel Amanda Crider Chirayu D Pandya Anthony O Ahmed Anilkumar Pillai
Publish Date: 2015/04/26
Volume: 53, Issue: 4, Pages: 2090-2099
Abstract
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 cochaperones FKBP5 PTGES3 and BAG1 and inflammatory cytokines IL6 IL1β and IFNγ were examined in the postmortem middle frontal gyrus tissues of 13 ASD and 13 agematched controls by qRTPCR 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 IL1β and IFNγ 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
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