Reduced spinophilin but not microtubule-associated protein 2 expression in the hippocampal formation in schizophrenia and mood disorders: molecular evidence for a pathology of dendritic spines.
OBJECTIVE
Aberrant synaptic connectivity may underlie the involvement of the hippocampus in schizophrenia. There is reasonable neuropathological evidence for a presynaptic pathology but few studies of the postsynaptic component. This study tested the hypothesis that hippocampal dendritic pathology is also present in schizophrenia.


METHODS
Using in situ hybridization in sections of hippocampal formation from 10 patients with schizophrenia, 10 patients with mood disorders (three with bipolar disorder and seven with major depression), and 10 healthy comparison subjects, the authors examined the expression of two important dendritic genes: spinophilin, which serves as a marker of dendritic spines, and microtubule-associated protein 2 (MAP2), an overall dendritic marker.


RESULTS
The patients with schizophrenia had lower levels of spinophilin mRNA in CA4 (hilus), CA3, the subiculum, and the entorhinal cortex than did the normal comparison subjects. The mood disorder group showed similar differences from the comparison group. MAP2 and cyclophilin mRNA did not differ between the groups in any subfield.


CONCLUSIONS
Decreased spinophilin but unchanged MAP2 expression provides molecular evidence for a hippocampal dendritic pathology in schizophrenia that preferentially affects the spines. As spines are the target of most glutamatergic synapses, the data extend the evidence that excitatory synapses are particularly affected. Similar dendritic spine pathology may also occur in mood disorders.
University Department of Psychiatry, Neurosciences Building, Warneford Hospital, Oxford OX3 7JX, UK. amanda.law@psych.ox.ac.uk.
Amanda J
AJ
Law
Cynthia Shannon
CS
Weickert
Thomas M
TM
Hyde
Joel E
JE
Kleinman
Paul J
PJ
Harrison
D000328:Adult; D000368:Aged; D001345:Autoradiography; D015331:Cohort Studies; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000099273:Neurabins
D021983:Cyclophilins; D005819:Genetic Markers; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000099273:Neurabins; C489788:MAP2 protein, human