Reelin signaling is impaired in autism

S. Hossein Fatemi, Anne V. Snow, Joel M. Stary, Mohsen Araghi-Niknam, Teri J. Reutiman, Suzanne Lee, Andrew I. Brooks, David A. Pearce

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

Abstract

Background: Autism is a severe neurodevelopmental disorder with genetic and environmental etiologies. Recent genetic linkage studies implicate Reelin glycoprotein in causation of autism. To further investigate these studies, brain levels of Reelin protein and mRNA and mRNAs for VLDLR, Dab-1, and GSK3 were investigated. Methods: Postmortem superior frontal, parietal, and cerebellar cortices of age, gender, and postmortem interval-matched autistic and control subjects were subjected to SDS-PAGE and Western blotting of Reelin protein. Quantitative reverse transcriptase polymerase chain reaction analysis of Reelin, VLDL-R, Dab-1, and GSK3 mRNA species in superior frontal and cerebellar cortices of autistic and control subjects were also performed. Results: Reelin 410, 330, and 180 kDa/β-actin values were reduced significantly in frontal and cerebellar, and nonsignificantly in parietal, areas of autistic brains versus control subjects, respectively. The mRNAs for Reln and Dab-1 were reduced significantly whereas the mRNA for Reln receptor VLDLR was elevated significantly in superior frontal and cerebellar areas of autistic brains versus control brains, respectively. Conclusions: Reductions in Reelin protein and mRNA and Dab 1 mRNA and elevations in Reln receptor VLDLR mRNA demonstrate impairments in the Reelin signaling system in autism, accounting for some of the brain structural and cognitive deficits observed in the disorder.

Original languageEnglish (US)
Pages (from-to)777-787
Number of pages11
JournalBiological psychiatry
Volume57
Issue number7
DOIs
StatePublished - Mar 15 2005

Bibliographical note

Funding Information:
This work was supported by the March of Dimes (SHF), the Jonty Foundation (SHF), and the Kunin Fund of St. Paul Foundation. We are grateful to Dr. Andre Goffinet for his generous gift of antiReelin antibody. We thank the TARF and affiliated brain banks (Harvard University Brain Bank, Universities of Miami and Maryland Brain Banks) for the gift of brain specimens. We are thankful to Ms. Laurie Iversen for diligent secretarial assistance

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Autism
  • Bipolar disorder
  • Cerebellum
  • Dab-1
  • GSK-3β
  • Parietal cortex
  • QPCR
  • Reelin
  • Schizophrenia
  • Superior frontal cortex
  • VLDLR
  • Western blotting
  • mRNA
  • β-actin

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