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

doi:10.1016/j.biopsych.2004.12.018

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 journal › Article › peer-review

225 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 language	English (US)
Pages (from-to)	777-787
Number of pages	11
Journal	Biological Psychiatry
Volume	57
Issue number	7
DOIs	https://doi.org/10.1016/j.biopsych.2004.12.018
State	Published - Mar 15 2005
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biological Psychiatry

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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10.1016/j.biopsych.2004.12.018

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@article{8a40fe2f620a40dda55921621c6b6172,

title = "Reelin signaling is impaired in autism",

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.",

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

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

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",

year = "2005",

month = mar,

day = "15",

doi = "10.1016/j.biopsych.2004.12.018",

language = "English (US)",

volume = "57",

pages = "777--787",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier Inc.",

number = "7",

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TY - JOUR

T1 - Reelin signaling is impaired in autism

AU - Fatemi, S. Hossein

AU - Snow, Anne V.

AU - Stary, Joel M.

AU - Araghi-Niknam, Mohsen

AU - Reutiman, Teri J.

AU - Lee, Suzanne

AU - Brooks, Andrew I.

AU - Pearce, David A.

N1 - 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

PY - 2005/3/15

Y1 - 2005/3/15

N2 - 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.

AB - 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.

KW - Autism

KW - Bipolar disorder

KW - Cerebellum

KW - Dab-1

KW - GSK-3β

KW - Parietal cortex

KW - QPCR

KW - Reelin

KW - Schizophrenia

KW - Superior frontal cortex

KW - VLDLR

KW - Western blotting

KW - mRNA

KW - β-actin

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U2 - 10.1016/j.biopsych.2004.12.018

DO - 10.1016/j.biopsych.2004.12.018

M3 - Article

C2 - 15820235

AN - SCOPUS:16844370707

SN - 0006-3223

VL - 57

SP - 777

EP - 787

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 7

ER -

Reelin signaling is impaired in autism

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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