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Antipsychotic treatment and neuregulin 1-ErbB4 signalling in schizophrenia
Authors:Pan Bo  Huang Xu-Feng  Deng Chao
Institution:
  • a Centre for Translational Neuroscience, School of Health Sciences, University of Wollongong, Wollongong, 2522 NSW, Australia
  • b Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, 2522 NSW, Australia
  • c Schizophrenia Research Institute, 384 Victoria Street, Darlinghurst, 2010, NSW Australia
  • Abstract:Evidence 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.
    Keywords:5-HT  serotonin  BA  Brodmann areas  BACE1  a transmembrane endopeptidase β-site APP-cleaving enzyme 1  CNS  central nervous system  CYT  C-terminal cytoplasmic tails  ErbB4  membrane-associated tyrosine kinases  ErbB4 receptor kinases  EGF  epidermal growth factor  Ig  immunoglobulin  GABA  γ-Aminobutyric acid  GPCRs  G-protein couple receptors  NMDA  N-methyl-D-aspartate  NRG1  neuregulin 1  PBLs  peripheral blood lymphocytes  PFC  prefrontal cortex  PPI  prepulse inhibition  PSD95  post synaptic density protein 95  SNP  single-nucleotide polymorphism  TACE  tumour necrosis factor-α converting enzyme  TMc  transmembrane domain
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