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Schizophrenia: more evidence for less glutamate
Paul D Morrison1, Lyn S Pilowsky
1Institute of Psychiatry, De Crespigny Hill, London SE5 8AF, UK.
Expert Review of Neurotherapeutics
|December 26, 2006
Summary
Schizophrenia may involve N-methyl-D-aspartate (NMDA) receptor deficits. This study found altered neuregulin 1 (NRG1)-ErbB4 signaling in schizophrenic brains, enhancing NMDA receptor inhibition.
Area of Science:
- Neuroscience
- Molecular Psychiatry
- Neurobiology
Background:
- Schizophrenia is potentially linked to glutamate transmission deficits at N-methyl-D-aspartate (NMDA) receptors.
- Neuregulin 1 (NRG1) signaling through ErbB4 receptors is known to inhibit NMDA receptor activity.
- NRG1 is a significant susceptibility gene for schizophrenia.
Purpose of the Study:
- To investigate the role of Neuregulin 1 (NRG1)-ErbB4 signaling in N-methyl-D-aspartate (NMDA) receptor function in schizophrenia.
- To compare NRG1-ErbB4 signaling and NMDA receptor activity between control and schizophrenic brains.
Main Methods:
- Comparative analysis of NMDA receptor responses in prefrontal cortex tissue from schizophrenic patients and controls.
- Assessment of NMDA receptor sensitivity to NRG1.
- Examination of the ErbB4-PSD-95-NMDA receptor complex coupling and NRG1-mediated ErbB4 stimulation.
Main Results:
- NMDA receptors in schizophrenic prefrontal cortex exhibited reduced responses to NMDA/glycine.
- Schizophrenic brain NMDA receptors showed increased sensitivity to the inhibitory effects of NRG1.
- The ErbB4-PSD-95-NMDA complex was more tightly coupled in schizophrenic brains, with enhanced NRG1-mediated ErbB4 stimulation.
Conclusions:
- Altered neuregulin 1 (NRG1)-ErbB4 signaling contributes to N-methyl-D-aspartate (NMDA) receptor hypofunction in schizophrenia.
- Findings support the importance of NMDA receptors in schizophrenia pathophysiology.
- These results suggest potential therapeutic strategies targeting glutamate transmission enhancement.
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