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Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
Asymmetrical reductions of hippocampal NMDAR1 glutamate receptor mRNA in the psychoses
1Department of Neuropathology, University of Oxford, Radcliffe Infirmary, Gibson Building, Woodstock Road, Oxford, OX2 6HE, UK.
Abstract:
The psychotomimetic properties of NMDA glutamate receptor antagonists suggest there may be disease related changes of this receptor in schizophrenia. Using in situ hybridisation histochemistry (ISHH), we measured mRNA for the obligatory NMDAR1 subunit of the NMDA glutamate receptor in post-mortem samples of hippocampus from schizophrenics, depressives, bipolar patients and normal controls. A significant main effect of diagnosis was observed in the dentate gyrus (ANOVA, p = 0.004) and a trend in the CA3 region (ANOVA, p = 0.06), with all psychiatric groups having reduced NMDAR1 mRNA levels compared to normal controls. In contrast to the affectively ill groups, the reductions in schizophrenics were more pronounced in the left side compared to the right. Expression of poly A mRNA also showed left-sided losses in the dentate gyrus in schizophrenia but reductions in NMDAR1 remained significant when expressed as a ratio of poly A. The findings confirm a recent report of reduced hippocampal NMDAR1 mRNA in schizophrenia. However, our new evidence suggests that this is a feature of both affective and schizophrenic disorders and that schizophrenia is distinguished from the others by left-sided reductions in hippocampal NMDAR1 gene expression.
Insights
Schizophrenia and other psychiatric disorders show reduced NMDAR1 mRNA in the hippocampus. Schizophrenia is uniquely characterized by left-sided reductions in this gene expression, distinguishing it from affective disorders.
Area of Science:
- Neuroscience
- Psychiatry
- Molecular Biology
Background:
- NMDA glutamate receptor antagonists exhibit psychotomimetic properties, suggesting potential alterations in schizophrenia.
- The NMDAR1 subunit is crucial for NMDA receptor function.
Purpose of the Study:
- To investigate NMDAR1 mRNA levels in the hippocampus of individuals with schizophrenia, depression, bipolar disorder, and healthy controls.
- To determine if reduced NMDAR1 mRNA is specific to schizophrenia or a broader feature of psychiatric illness.
Main Methods:
- In situ hybridisation histochemistry (ISHH) was employed to quantify NMDAR1 mRNA in post-mortem hippocampal samples.
- Analysis included diagnostic groups (schizophrenia, depression, bipolar disorder, controls) and regional comparisons (dentate gyrus, CA3).
Main Results:
- All psychiatric groups exhibited reduced NMDAR1 mRNA levels in the dentate gyrus and CA3 regions compared to controls.
- Schizophrenia showed more pronounced left-sided reductions in NMDAR1 mRNA compared to affective disorders.
- Left-sided losses in poly A mRNA were observed in the dentate gyrus in schizophrenia, but NMDAR1 reductions remained significant when normalized.
Conclusions:
- Reduced hippocampal NMDAR1 mRNA is a common feature in schizophrenia, depression, and bipolar disorder.
- Schizophrenia is distinguished by left-sided reductions in hippocampal NMDAR1 gene expression, differentiating it from affective disorders.
