Antipsychotic treatment and neuregulin 1 -ErbB4 signalling in schizophreniaFaculty of Health and Behavioural Sciences - Papers (Archive)
AbstractEvidence from genetic, transgenic and post-mortem studies has strongly supported the critical role that neuregulin 1 (NRG1) and its ErbB4 receptor plays in the pathophysiology of schizophrenia. This article aims to review current evidence regarding the effects of antipsychotic treatment on NRG1–ErbB4 signalling. NRG1 and ErbB4 knockout mice display abnormal behaviours relevant to certain features of schizophrenia, which could be improved by antipsychotic (clozapine/haloperidol) treatment. In contrast to most NRG1/ErbB4 knockout mice with a decreased NRG1–ErbB4 signalling, the majority post-mortem studies showed an increased NRG1–ErbB4 signalling in schizophrenic patients. These differences could be due to degrees of alteration in risk genes (subtle variations in patients vs pronounced alteration in mutant mice) or the duration of the modification on NRG1 signalling. Various antipsychotics have different effects on NRG1 and ErbB4 expression and signalling that are dependent on treatment duration. Current evidence suggests that a chronic (12 weeks) antipsychotic treatment, at least in animal models, could downregulate NRG1–ErbB4 signalling, although an upregulation is seen for a short-term treatment. These effects may be due to multiple binding profiles with various G-coupled protein receptors (e.g. dopamine, and serotonin receptors) of antipsychotics. Studies are needed to investigate the interactions between NRG1–ErbB4 and the other signalling pathways (such as glutamatergic, GABAergic and dopaminergic). Furthermore, the interactions between NRG1/ErbB4 and other schizophrenia suspensibility genes under antipsychotic treatment also require investigation.
Additional Grant Numberhttp://purl.org/au-research/grants/NHMRC/573426
Citation InformationBo Pan, Xu-Feng Huang and Chao Deng. "Antipsychotic treatment and neuregulin 1 -ErbB4 signalling in schizophrenia" (2011) p. 924 - 930
Available at: http://works.bepress.com/xhuang/90/