Altered mRNA Levels of Glucocorticoid Receptor, Mineralocorticoid Receptor, and Co-Chaperones (FKBP5 and PTGES3) in the Middle Frontal Gyrus of Autism Spectrum Disorder Subjects

Neil Patel, Amanda Crider, Chirayukumar D Pandya, Anthony O. Ahmed, Anilkumar R Pillai

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)2090-2099
Number of pages10
JournalMolecular Neurobiology
Volume53
Issue number4
DOIs
StatePublished - May 1 2016

Fingerprint

Mineralocorticoid Receptors
Glucocorticoid Receptors
Autistic Disorder
Messenger RNA
Interleukin-1
Autism Spectrum Disorder
Cytokines
Interleukin-6
Protein Isoforms
Proteins
Western Blotting
Inflammation

Keywords

  • Autism
  • Brain
  • Glucocorticoid
  • Mineralocorticoid
  • Receptor
  • Stress

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Altered mRNA Levels of Glucocorticoid Receptor, Mineralocorticoid Receptor, and Co-Chaperones (FKBP5 and PTGES3) in the Middle Frontal Gyrus of Autism Spectrum Disorder Subjects. / Patel, Neil; Crider, Amanda; Pandya, Chirayukumar D; Ahmed, Anthony O.; Pillai, Anilkumar R.

In: Molecular Neurobiology, Vol. 53, No. 4, 01.05.2016, p. 2090-2099.

Research output: Contribution to journalArticle

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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 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.",
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