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Molecular Neurobiology

, Volume 53, Issue 4, pp 2090–2099 | Cite as

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
  • Chirayu D. Pandya
  • Anthony O. Ahmed
  • Anilkumar PillaiEmail author
Article

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.

Keywords

Autism Brain Stress Glucocorticoid Receptor Mineralocorticoid 

Abbreviations

ADI-R

Autism diagnostic interview revised

ASD

Autism spectrum disorders

BAG1

BCL2-associated athanogene

GRα

Glucocorticoid receptor alpha

FKBP5

FK506 binding protein 51

IFN-γ

Interferon-gamma

IL-1β

Interleukin-1beta

IL-6

Interleukin-6

GRβ

Glucocorticoid receptor beta

GRγ

Glucocorticoid receptor gamma

GRP

Glucocorticoid receptor P

PTGES3

Prostaglandin E synthase 3 (cytosolic)

MR

Mineralocorticoid receptor

Notes

Acknowledgments

The authors would like to thank Diya Peter for her technical assistance. Human postmortem samples were obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD. The Bank is funded by NIH Contract No. #HHSN275200900011C, Ref. No. NO1-HD-9-0011.

Conflict of Interest

The author(s) declare that they have no competing interests.

Author Contributions

NP and AC carried out the gene expression studies. CDP and AC performed the protein analysis. AOA carried out the statistical analysis and helped to draft the manuscript. AP designed the study and wrote the manuscript. All authors read and approved the final manuscript.

Supplementary material

12035_2015_9178_MOESM1_ESM.docx (15 kb)
Additional file 1: Table S1 List of primers used in the qRT-PCR. (DOCX 15 kb)
12035_2015_9178_MOESM2_ESM.docx (16 kb)
Additional file 2: Table S2 Correlations of mRNA transcripts with confounding variables. (DOCX 15 kb)
12035_2015_9178_MOESM3_ESM.docx (19 kb)
Additional file 3: Table S3 Correlations between stress-related mRNA transcripts. (DOCX 18 kb)
12035_2015_9178_MOESM4_ESM.docx (14 kb)
Additional file 4: Table S4 Correlation between cytokine and stress-related mRNA transcripts. (DOCX 14 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Neil Patel
    • 1
  • Amanda Crider
    • 1
  • Chirayu D. Pandya
    • 1
  • Anthony O. Ahmed
    • 2
  • Anilkumar Pillai
    • 1
    Email author
  1. 1.Department of Psychiatry and Health Behavior, Medical College of GeorgiaGeorgia Regents UniversityAugustaUSA
  2. 2.Department of PsychiatryWeill Cornell Medical CollegeWhite PlainsUSA

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