Schizophrenia: more evidence for less glutamate.
Evaluation of: Hahn CJ, Hoau-Yan W, Dan-Sung C et al. Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat. Med. 12, 824-828 (2006). Schizophrenia may be associated with deficits in glutamate transmission at the N-methyl-D-aspartate (NMDA) receptor complex. Recent work has shown that neuregulin 1 (NRG1) acts via ErbB4 receptors to inhibit NMDA receptor currents. This is important given that NRG1 is a convincing susceptibility gene in schizophrenia. Hahn and colleagues add to our knowledge of NRG1 modulation of NMDA receptors and show intriguing differences between control and schizophrenic brains. NMDA receptors in the schizophrenic prefrontal cortex showed smaller responses to exogenously applied NMDA/glycine. Furthermore, NMDA receptors in tissue from schizophrenic patients appeared to be more sensitive to the inhibitory effects of a fixed dose of NRG1. In agreement, the ErbB4-PSD-95-NMDA complex was more tightly coupled in schizophrenic brains and NRG1-mediated stimulation of ErbB4 was markedly enhanced. These findings underscore the importance of NMDA receptors in schizophrenia and support therapeutic strategies aimed at boosting glutamate transmission.
Morrison
Paul D
PD
Institute of Psychiatry, De Crespigny Hill, London SE5 8AF, UK.
Pilowsky
Lyn S
LS
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002102:Cadaver; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism*; D019317:Evidence-Based Medicine / Q000379:methods / Q000639:trends; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D020890:Neuregulin-1 / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D066247:Receptor, ErbB-4; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
D020890:Neuregulin-1; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4