文献类型：期刊文献

英文题名：Guanosine ameliorates positive symptoms of schizophrenia via modulating 5-HT1A and 5-HT2A receptors

作者：Mao, Yu[1];Xing, Yao[1];Jie Li[1];Dong, Dong[1];Zhang, Shoude[1,3];Zhao, Zhenjiang[1];Xie, Jingli[2];Wang, Rui[1];Li, Honglin[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Coll Bioengn, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Qinghai Univ, Med Coll, Dept Pharm, State Key Lab Plateau Ecol & Agr, Xining 810016, Qinghai, Peoples R China

年份：2021

卷号：13

期号：5

起止页码：4040

外文期刊名：AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH

收录：;WOS:【SSCI(收录号:WOS:000656707400008)，SCI-EXPANDED(收录号:WOS:000656707400008)】；

基金：The research is supported in part by the National Key Research and Development Program (Grant 2016YFA0502304) , the National Natural Science Foundation of China (grant 81825020) . Honglin Li is also sponsored by National Program for Special Supports of Eminent Professionals and National Program for Support of TopNotch Young Professionals.

语种：英文

外文关键词：Guanosine; schizophrenia; 5-HT1A receptor; 5-HT2A receptor; PI3K/Akt

摘要：Schizophrenia is a serious mental disorder characterized by hallucinations, delusions, and extremely disordered thinking and behavior. There are several hypotheses of pathogenesis in schizophrenia: dopaminergic, glutamatergic, or serotonergic hyperfunction. Guanosine reportedly protects the central nervous system by modulating the glutamatergic system. Thus, we assumed that guanosine may exert a positive effect on the pathophysiology of schizophrenia. Herein, we demonstrated that guanosine significantly reduced MK-801-induced hyperlocomotion and stereotyped behaviors, but showed no effect on hyperlocomotion induced by d-amphetamine, indicating that guanosine may directly affect the glutamatergic system. Guanosine dose-dependently reduced 5-HTP-induced wet dog shakes (WDS) and other serotonin syndromes (SS) behaviors, indicating that it might block serotonin 5-HT1A or 5-HT2A receptors. Finally, we confirm that that guanosine modulates serotonin 5-HT1A and 5-HT2A receptors and it might be anti-schizophrenic partly through pertussis toxin-sensitive G(i/o)-coupled PI3K/Akt signaling. Collectively, this study provides possible compounds and mechanisms for therapeutic effects on schizophrenia.