Enhancement of effect of risperidone on cognitive function of schizophrenic mice by fluoxetine  

作　　者：QIAO Ying ZHANG Lei HE Shen SHENG Jian-hua WANG Hui-fang LI Hua-fang 

机构地区：[1]Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China [2]Basic MedicineFaculty of Shanghai Jiao Tong University, Shanghai 200025, China

出　　处：《上海交通大学学报（医学版）》2015年第10期1436-1442,共7页Journal of Shanghai Jiao tong University:Medical Science

基　　金：Special Project from Ministry of Science and Technology of China(2012ZX09303-003);Shanghai Natural Science Foundation(13ZR1435800);Training Project of Excellent Talents in Shanghai(XBR2011049)

摘　　要：Objective To explore the molecular mechanism of enhancing the effect of risperidone on the cognitive function of schizophrenic mice by fluoxetine. Methods Schizophrenic mice were injected with M K-801 and drugs( fluoxetine and / or risperidone) were adm inistrated orally 30 min before the injection of M K-801.Mice of the control group adm inistrated the same dose of norm al saline. The cognitive function, distance of activity, and stereotyped behavior of mice were observed. The expressions of key param eters of MEK / ERK pathway in hippocam pus were detected by Western blotting or real-time qPCR. The participation of MEK / ERK pathway in isolated hippocam palneuron injuries induced by M K-801 mediation was also analyzed. Results The mice of M K-801 group showed prolonged activity distance, increased stereotyped behavior scores, and cognitive im pairm ent. Expressions of pMEK/MEK, pERK/ERK1 /2, MMP2 /9, and TIMP1 /2 of the MK-801 group increased. The aforem entioned proteins of drug adm inistration groups decreased dram atically. For schizophrenic m ice, fluoxetine enhanced effects of risperidone in norm alizing abnorm al behaviors, affecting cognitive function, and unusual protein expressions( P < 0. 05). Results of in vitro experim ents were sim ilar to those of in vivo experim ents. Conclusion Fluoxetine enhances the anti-schizophrenic effect of risperidone by norm alizing the activated MEK / ERK signaling pathway.Objective To explore the molecular mechanism of enhancing the effect of risperidone on the cognitive funcdon of schizophrenic mice by fluoxetine. Methods Schizophrenic mice were injected with MK- 801 and drugs （finoxetine and/or risperidone） were administrated orally 30 min before the injection of MK-801. Mice of the control group administrated the same dose of normal saline. The cognitive function, distance of activity, and stereotyped behavior of mice were observed. The expressions of key parameters of MEK/ERK pathway in hippocampus were detected by Western blotting or real-time qPCR. The participation of MEK/ERK pathway in isolated hippocampal neuron injuries induced by MK-801 mediation was also analyzed. Results The mice of MK-801 group showed prolonged activity distance, increased stereotyped behavior scores, and cognitive impairment. Expressions of pMEK/MEK, pERK/ERK1/2, MMP2/9, and TIMP1/2 of the MK-801 group increased. The aforementioned proteins of drug administration groups decreased dramatically. For schizophrenic mice, fluoxetine enhanced effects of risperidone in normalizing abnormal behaviors, affecting cognitive function, and unusual protein expressions （P〈0.05）. Results of in vitro experiments were similar to those of in vivo experiments. Conclusion Fluoxetine enhances the anti-schizophrenic effect of risperidone by normalizing the activated MEK/ERK signaling pathway.

关 键 词：SCHIZOPHRENIA cognitive dysfunction MK-801 MEK/ERK pathway matrix metaUoproteinase conncxins 

分 类 号：R749.3[医药卫生—神经病学与精神病学]