title: Effects of prolonged antipsychotic administration on neuregulin-1/ErbB signaling in rat prefrontal cortex and myocardium: implications for the therapeutic action and cardiac adverse effect.
abstract: Patients with schizophrenia (SCZ) are at higher risk for developing cardiovascular disease (CVD) and neuregulin-1 (NRG1)/ErbB signaling has been identified as a common susceptibility pathway for the comorbidity. Antipsychotic treatment can change NRG1/ErbB signaling in the brain, which has been implicated in their therapeutic actions, whereas the drug-induced alterations of NRG1/ErbB pathway in cardiovascular system might be associated with the prominent cardiac side-effects of antipsychotic medication. To test this hypothesis, we examined NRG1/ErbB system in rat prefrontal cortex (PFC) and myocardium following 4-week intraperitoneal administration of haloperidol, risperidone or clozapine. Generally, the antipsychotics significantly enhanced NRG1/ErbB signaling with increased expression of NRG1 and phosphorylation of ErbB4 and ErbB2 in the brain and myocardium, except that clozapine partly blocked the cardiac NRG1/ErbB2 activation, which could be associated with its more severe cardiac adverse actions. Combined, our data firstly showed evidence of the effect of antipsychotic exposure on myocardial NRG1/ErbB signaling, along with the activated NRG1/ErbB system in brain, providing a potential link between the therapeutic actions and cardiotoxicity.
authors.affiliation: Institute of Clinical Pharmacy, Jining First People's Hospital of Jining Medical University, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Dang
authors.forename: Yujin
authors.initials: Y
authors.lastname: Guo
authors.forename: Hualin
authors.initials: H
authors.lastname: Cai
authors.forename: Ranyao
authors.initials: R
authors.lastname: Yang
authors.forename: Donglou
authors.initials: D
authors.lastname: Liang
authors.forename: Chuanfeng
authors.initials: C
authors.lastname: Lv
authors.forename: Pei
authors.initials: P
authors.lastname: Jiang
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects*; D015897:Comorbidity; D020022:Genetic Predisposition to Disease; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects*; D007274:Injections, Intraperitoneal; D008297:Male; D009206:Myocardium; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D066247:Receptor, ErbB-4 / Q000235:genetics / Q000378:metabolism; D012306:Risk; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects*; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; D018967:Risperidone; C490580:Nrg1 protein, rat; C483804:Erbb2 protein, rat; C587691:Erbb4 protein, rat