Reelin signaling is impaired in autism

• Published in: Biological psychiatry (1969) Vol. 57; no. 7; pp. 777 - 787
• Main Authors: Fatemi, S. Hossein, Snow, Anne V., Stary, Joel M., Araghi-Niknam, Mohsen, Reutiman, Teri J., Lee, Suzanne, Brooks, Andrew I., Pearce, David A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2005; Elsevier Science
• Subjects: Actins - metabolism; Adaptor Proteins, Signal Transducing; Adult; Adult and adolescent clinical studies; Age Factors; autism; Autistic Disorder - genetics; Autistic Disorder - metabolism; Biological and medical sciences; bipolar disorder; Blotting, Western - methods; Case-Control Studies; Cell Adhesion Molecules, Neuronal - genetics; Cell Adhesion Molecules, Neuronal - metabolism; cerebellum; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Dab-1; Electrophoretic Mobility Shift Assay - methods; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Female; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; GSK-3β; Humans; Male; Medical sciences; Miscellaneous; Models, Biological; mRNA; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; parietal cortex; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; QPCR; Receptors, LDL - genetics; Receptors, LDL - metabolism; Reelin; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; schizophrenia; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Sex Factors; Signal Transduction - physiology; superior frontal cortex; VLDLR; Western blotting; β-actin; Dab-1; QPCR; β-actin; mRNA; parietal cortex; schizophrenia; VLDLR; autism; cerebellum; Western blotting; GSK-3β; bipolar disorder; Reelin; superior frontal cortex; Mood disorder; Cerebellum; Human; Schizophrenia; Bipolar disorder; Developmental disorder; Frontal cortex; Psychosis; Autism; Signal transduction; Messenger RNA; Actin; Parietal cortex; Immunoblotting assay
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2004.12.018

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. 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. 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. 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.