Cellular Basis of Reduced Cortical Reelin Expression in Schizophrenia

• Published in: The American journal of psychiatry Vol. 163; no. 3; pp. 540 - 542
• Main Authors: Eastwood, Sharon L., Harrison, Paul J.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Publishing 01.03.2006; American Psychiatric Association
• Subjects: Adult and adolescent clinical studies; Biological and medical sciences; Brain; Cell Adhesion Molecules, Neuronal - genetics; Cell Adhesion Molecules, Neuronal - metabolism; Cellular biology; Cerebral Cortex - metabolism; Dentate Gyrus - metabolism; Down-Regulation; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Female; GAP-43 Protein - genetics; GAP-43 Protein - metabolism; Gene Expression; Hippocampus - metabolism; Humans; Interneurons - metabolism; Male; Medical sciences; Middle Aged; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons; Neurons - metabolism; Parahippocampal Gyrus - metabolism; Pathology; Prefrontal Cortex - metabolism; Proteins; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; RNA, Messenger - metabolism; Schizophrenia; Schizophrenia - genetics; Schizophrenia - metabolism; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Synaptophysin - genetics; Synaptophysin - metabolism; Vesicular Glutamate Transport Protein 1 - genetics; Vesicular Glutamate Transport Protein 1 - metabolism; Psychosis; Schizophrenia; Reelin
• DOI: 10.1176/appi.ajp.163.3.540
• ISSN: 0002-953X

OBJECTIVE: The authors' goals were to establish the cellular origin of the reduced cortical reelin expression that occurs in schizophrenia and to relate it to markers of synaptic pathology. METHOD: In situ hybridization was used to quantify reelin mRNA in the hippocampal formation and dorsolateral prefrontal cortex of brains from 13 subjects with schizophrenia and 12 subjects without schizophrenia. Results were correlated with the expression of three synaptic protein genes in the dentate gyrus. RESULTS: Reelin mRNA was expressed by layer I neurons, interneurons, and interstitial white matter neurons. In subjects with schizophrenia, less reelin mRNA was expressed by interstitial white matter neurons in the hippocampal formation and by all three cell types in the prefrontal cortex. Reelin and synaptic protein expression correlated positively. CONCLUSIONS: Interstitial white matter neurons, presumed remnants of the cortical subplate, contribute to the reduction in reelin mRNA in schizophrenia. Down-regulation of reelin expression may in turn contribute to the synaptic pathology of the disorder.