Reelin mrna is significantly decreased (-50%) in several areas of schizophrenic brain

During embryonic development, neuronal migration and positioning is regulated by a protein named Reelin secreted by GABAergic marginal zone neurons (Cajal Retzius cells) that undergo apoptosis shortly after birth. Reelin is secreted in the extracellular matrix and uses an intracellular phosphoprotein, the mouse disabled-1 (mDab-1) gene product in its signaling cascade. In fact the neurological phenotype caused by a genetic defect of either Reelin or mDab-1 is similar. We have shown earlier that Reelin mRNA is expressed in adult human brain. We also demonstrated that in the laminated telencephalic structures, reelin rnRNA is almost exclusively expressed in GABAergic neurons, whereas in cerebellum is expressed in glutamatergic granule neurons. Using a quantitative RT-PCR assay, we studied Reelin mRNA expression in the postmortem brain of schizophrenics and matched controls and found that in telencephalon, hippocampus, striatum and cerebellum of schizophrenic brain*, Reelin expression is decreased of about 50%. We are presently investigating whether the expression of mDab-1 is also altered in brains of schizophrenics. DNA polymorphisms in Reelin gene exists in several schizophrenic family pedigrees. It is, therefore, possible that the decreased expression of Reelin mRNA in different brain regions detected in post-mortem schizophrenic brains, might reflect one of the genetic abnormalities underpinning the neuropamology of this disease. * Tissue specimens were obtained from the a) National Neurological Research Specimen Bank; b) Harvard Brain Tissue Resource Center; c) Clinical Brain Disorder Branch, IRP, NIMH.