Cellular basis of reduced cortical reelin expression in schizophrenia.
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.


METHODS
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.
Eastwood
Sharon L
SL
Department of Psychiatry, University of Oxford, Oxford OX3 7JX, UK. sharon.eastwood@psych.ox.ac.uk
Harrison
Paul J
PJ
D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007395:Interneurons / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D020534:Parahippocampal Gyrus / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000091042:Reelin Protein; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000091042:Reelin Protein; C493464:SLC17A7 protein, human; D016708:Synaptophysin; D050598:Vesicular Glutamate Transport Protein 1; C000717127:RELN protein, human; D012697:Serine Endopeptidases