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/beta-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.