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Gene expression and neuronal activity in schizophrenia: a study of polyadenylated mRNA in the hippocampal formation
P J Harrison1, P W Burnet, P Falkai
1Department of Psychiatry, Warneford Hospital, University of Oxford, UK. paul.harrison@psychiatry.ox.ac.uk
Abstract:
The abundance of polyadenylated messenger RNA (poly(A)+mRNA) reflects overall gene expression and provides an index on neuronal activity. Poly(A)+mRNA was measured in the hippocampal formation and in occipital, temporal, cingulate and frontal cortices (Brodmann areas 17, 22, 24 and 46, respectively) of 11 schizophrenic and 17 control subjects post mortem by in situ hybridization histochemistry with a 35S-oligodeoxythymidine probe. There were no differences in poly(A)+mRNA between cases and controls, except for a modest decrease in the parahippocampal gyrus of the schizophrenics which may be attributable to cytoarchitectural differences in this area in the disease. The unchanged level of poly(A)+mRNA in all other regions argues against the existence of a widespread or sustained alteration in the metabolic activity of cortical neurons in schizophrenia. It also provides a further indication that the differential expression of individual transcripts reported in the disease is not merely reflecting changes in overall gene expression.
Insights
Investigating gene expression in schizophrenia, this study found no widespread changes in polyadenylated messenger RNA (poly(A)+mRNA) levels in the brain. A minor decrease in one region suggests localized effects rather than global neuronal alterations.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Polyadenylated messenger RNA (poly(A)+mRNA) levels serve as an indicator of overall gene expression and neuronal activity.
- Schizophrenia is a complex psychiatric disorder with suspected alterations in gene expression within the brain.
Purpose of the Study:
- To investigate whether schizophrenia is associated with widespread changes in poly(A)+mRNA abundance in key brain regions.
- To determine if observed differential gene expression in schizophrenia reflects global changes in neuronal metabolic activity.
Main Methods:
- Postmortem brain tissue from 11 schizophrenic subjects and 17 controls was analyzed.
- Poly(A)+mRNA levels were quantified in the hippocampal formation and specific cortical areas (Brodmann areas 17, 22, 24, 46) using in situ hybridization histochemistry.
Main Results:
- No significant differences in poly(A)+mRNA levels were found between schizophrenic patients and controls in most brain regions examined.
- A modest decrease in poly(A)+mRNA was observed in the parahippocampal gyrus of schizophrenic subjects, potentially due to cytoarchitectural differences.
- The findings suggest that widespread alterations in neuronal metabolic activity are unlikely in schizophrenia.
Conclusions:
- The study provides evidence against a global deficit in gene expression or neuronal activity in schizophrenia.
- Observed transcript-specific changes in schizophrenia are likely not a consequence of broad alterations in overall gene expression.