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/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.
authors.affiliation: Department of Psychiatry, Division of Neuroscience Research, University of Minnesota, Minneapolis, MN 55455, USA. fatem002@umn.edu
authors.forename: S Hossein
authors.initials: SH
authors.lastname: Fatemi
authors.forename: Anne V
authors.initials: AV
authors.lastname: Snow
authors.forename: Joel M
authors.initials: JM
authors.lastname: Stary
authors.forename: Mohsen
authors.initials: M
authors.lastname: Araghi-Niknam
authors.forename: Teri J
authors.initials: TJ
authors.lastname: Reutiman
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lee
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Brooks
authors.forename: David A
authors.initials: DA
authors.lastname: Pearce
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000367:Age Factors; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015816:Cell Adhesion Molecules, Neuronal; C115785:DAB1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; D038362:Glycogen Synthase Kinase 3; C000717127:RELN protein, human; D012697:Serine Endopeptidases