Explorative study on the expression of neuregulin-1 gene in peripheral blood of schizophrenia

Zhang, Hongxing; Zhao, Jingbo; Lv, Luxian; Li, Wenqiang; Xu, Lin; Ouyang, Xuan; Yuan, Zhiqing; Huang, Jinsong

doi:10.1016/j.neulet.2007.09.051

Cited by 47 publications

(42 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the same study, four-week treatment with risperidone increased the protein levels of both NRG1 isoforms and ErbB4 receptors in the hippocampus, but not in the PFC (Wang et al, 2008). Additionally, in a clinical study, after a 2-week treatment with risperidone and quetiapine, NRG1 mRNA expression of PBLs of first-onset schizophrenia patients (who has not take antipsychotics before) significantly increased compared to the levels before antipsychotic drug therapies (Zhang et al, 2008). Moreover, an in vitro study has shown that NRG1 protein expression increased in human fetal brain aggregates after being exposed to clozapine for three weeks; however, the expression of NRG1 proteins did not change following exposure to haloperidol (Chana et al, 2009).…”

Section: The Effects Of Antipsychotic Treatment On Nrg1-erbb4 Signallingmentioning

confidence: 88%

“…(2) Expression of type II increased in BA10. Petryshen et al, 2005 Expression of NRG1 type I and type III increased in PBLs of schizophrenia patients Zhang et al, 2008 NRG1 expression in PBLs of schizophrenia patients was lower than control groups before any antipsychotic treatment. Hahn et al, 2006 ErbB4 expression in the brain of schizophrenia patients did not change, but the phosphorylation of the ErbB4 receptor elevated.…”

Section: Hahn Et Al 2006mentioning

confidence: 97%

“…It was reported that the expression levels of NRG1 transcript variants in type I and type III isoforms significantly increased in peripheral blood lymphocytes (PBLs) from schizophrenia patients (Petryshen et al, 2005). However, another study reported a decrease of NRG1 mRNA expression in PBLs from schizophrenia patients (Zhang et al, 2008).…”

Section: Dysregulated Nrg1-erbb4 Signalling In Schizophrenia: Is It Cmentioning

confidence: 99%

See 2 more Smart Citations

Antipsychotic treatment and neuregulin 1–ErbB4 signalling in schizophrenia

Pan

Huang

Deng

2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

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. and ErbB4 knockout mice display some schizophrenia-like behavioural abnormalities, which could be improved by antipsychotic (clozapine/haloperidol) treatment. In contrast to NRG1/ErbB4 knockout mice with a decreased NRG1-ErbB4 signalling, the majority post-mortem studies showed an increased NRG1-ErbB4 signalling in schizophrenia 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 dependent on treatment duration. Current evidence suggests that a chronic (12 weeks) antipsychotic treatment, at least in animal models, downregulates NRG1-ErbB4 signalling, although an upregulation is seen for a short term treatment. Therefore, the dysfunctional NRG1-ErbB4 signalling observed in schizophrenia is unlikely to be due to antipsychotic therapy. Furthermore, multiple-receptor binding profiles (e.g. dopamine, and 5-HT receptors) of antipsychotics may also contribute to their different influences on NRG1-ErbB4 signalling. Studies are also needed to investigate the interactions between NRG1-ErbB4 and the other signalling pathways (such as glutamatergic, GABAergic and dopaminergic).

show abstract

Section: The Effects Of Antipsychotic Treatment On Nrg1-erbb4 Signallingmentioning

confidence: 88%

Section: Hahn Et Al 2006mentioning

confidence: 97%

Section: Dysregulated Nrg1-erbb4 Signalling In Schizophrenia: Is It Cmentioning

confidence: 99%

See 1 more Smart Citation

Antipsychotic treatment and neuregulin 1–ErbB4 signalling in schizophrenia

Pan

Huang

Deng

2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

show abstract

“…77 GABA plays a key role in the function of the prefrontal cortex, an area impaired in schizophrenia 78 and linked to negative symptoms and cognitive impairment, 79,80 including working memory, a core cognitive deficit in the illness. 81 Antipsychotic drugs can modify GABA and glutamate system elements, including GABA A receptor, extracellular GABA levels and expression, glutamate transporters, 82 and neuregulin-1 (which regulates the expression of NMDA and GABA A receptors), 83 as well as ionotropic and metabotropic glutamate receptors. 84,85 Interestingly, atypical antipsychotics differ from the typical ones in their effect on the GABA system, including hippocampal and cortical GABA A receptor density, 86 GABA transporter expression, 87 and GABA transporter levels.…”

Section: Clinical Relevancementioning

confidence: 99%

Multifunctional Pharmacotherapy: What Can We Learn from Study of Selective Serotonin Reuptake Inhibitor Augmentation of Antipsychotics in Negative-Symptom Schizophrenia?

et al. 2009

View full text Add to dashboard Cite

Summary: Many patients suffering from major psychiatric disorders do not respond adequately to monotherapy and require additional drugs. To date, there are no objective guidelines for deciding which combination may be effective, and the choice is based on previous clinical experience and on trial and error. Even when combination drugs are effective, the biochemical mechanisms responsible for the value-added effect are unknown. Understanding the mechanism of such synergism may provide a rational basis for choosing drug combinations and for developing more effective drugs. In schizophrenia, negative symptoms respond poorly to antipsychotics, but may improve when these are augmented with selective serotonin reuptake inhibitors (SSRI). This augmenting effect cannot be explained by summating the pharmacological effects of the individual drugs. We proposed that the study of SSRI augmentation can serve as a window to understanding the biochemical mechanisms of clinically effective drug synergism. In a series of studies we identified unique biochemical effects of the combination, different from each individual drug, and proposed that some of these are involved in mediating the clinical effect. Here we review some of the findings and propose that the mechanism of action involves regionally selective modulation of the GABA system. The evidence indicates that the SSRI antidepressant-antipsychotic combination may be a useful paradigm for studying therapeutically effective synergistic drug interactions in schizophrenia. Although as yet limited in scope, the findings of definable molecular targets for synergistic SSRIantipsychotic interaction provide new directions to inform future research and provide novel bio-molecular targets for drug development.

show abstract

“…Several studies have investigated the effects of some antipsychotics on the expression of NRG1 and ErbB4 receptors, however, those results were discrepant (Chana et al, 2009;Shibuya et al, 2010;Wang et al, 2008;Zhang et al, 2008). A previous study found that 4-week treatment with clozapine (10mg/kg, once/day, i.p.)…”

Section: Discussionmentioning

confidence: 99%

Differential effects of short- and long-term antipsychotic treatment on the expression of neuregulin-1 and ErbB4 receptors in the rat brain

Deng

Pan

et al. 2015

Psychiatry Research

View full text Add to dashboard Cite

Neuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for schizophrenia. Postmortem studies indicated that NRG1-ErbB4 signalling is impaired in schizophrenia subjects. This study investigated whether short-or long-term antipsychotic treatment has different effects on the expression of NRG1 and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either aripiprazole (0.75 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.5 mg/kg), or vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine the expression of NRG1 isoforms (135 kDa, 70 kDa and 40 kDa) and ErbB4 receptors. Both 1-week haloperidol and olanzapine treatment increased NRG1-70 kDa expression in the hippocampus; haloperidol also up-regulated ErbB4 levels in the prefrontal cortex (PFC). In the 12-week group, aripiprazole decreased the expression of all three NRG1 isoforms and ErbB4 receptors in the PFC, NRG1-70 kDa and -40 kDa in the cingulate cortex (Cg), and NRG1-135 kDa, -70 kDa and ErbB4 receptors in the hippocampus; haloperidol reduced NRG1-135 kDa in the PFC, NRG1-40 kDa in all three brain regions, and ErbB4 receptor levels in the PFC and hippocampus; NRG1-40 kDa in the PFC and Cg was also downregulated by olanzapine. These results suggest that the time-dependent and region-specific effects of antipsychotics on NRG1-ErbB4 signalling may contribute to the efficacy of antipsychotics to treat schizophrenia. AbstractNeuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for schizophrenia. Post-mortem studies indicated that NRG1-ErbB4 signalling is impaired in schizophrenia subjects. This study investigated whether short-or long-term antipsychotic treatment has different effects on the expression of NRG1 and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either aripiprazole (0.75mg/kg), haloperidol (0.1mg/kg), olanzapine (0.5mg/kg), or vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine the expression of NRG1 isoforms (135kDa, 70kDa and 40kDa) and ErbB4 receptors. Both 1-week haloperidol and olanzapine treatment increased NRG1-70kDa expression in the hippocampus; haloperidol also up-regulated ErbB4 levels in the prefrontal cortex (PFC). In the 12-week group, aripiprazole decreased the expression of all three NRG1 isoforms and ErbB4 receptors in the PFC, NRG1-70kDa and -40kDa in the cingulate cortex (Cg), and NRG1-135kDa, -70kDa and ErbB4 receptors in the hippocampus; haloperidol reduced NRG1-135kDa in the PFC, NRG1-40kDa in all three brain regions, and ErbB4 receptor levels in the PFC and hippocampus; NRG1-40kDa in the PFC and Cg was also down-regulated by olanzapine. These results suggest that the time-dependent and regionspecific effects of antipsychotics on NRG1-ErbB4 signalling may contribute to the efficacy of antipsychotics to treat schizophrenia.

show abstract

Explorative study on the expression of neuregulin-1 gene in peripheral blood of schizophrenia

Cited by 47 publications

References 23 publications

Antipsychotic treatment and neuregulin 1–ErbB4 signalling in schizophrenia

Antipsychotic treatment and neuregulin 1–ErbB4 signalling in schizophrenia

Multifunctional Pharmacotherapy: What Can We Learn from Study of Selective Serotonin Reuptake Inhibitor Augmentation of Antipsychotics in Negative-Symptom Schizophrenia?

Differential effects of short- and long-term antipsychotic treatment on the expression of neuregulin-1 and ErbB4 receptors in the rat brain

Contact Info

Product

Resources

About