Nicotine pretreatment alleviates MK-801-induced behavioral and cognitive deficits in mice by regulating Pdlim5/CRTC1 in the PFC  

作　　者：Qian Wang Meng-wei Wang Yan-yun Sun Xiao-yan Hu Pan-pan Geng Hui Shu Xiao-na Wang Hao Wang Jun-fang Zhang Hong-qiang Cheng Wei Wang Xin-chun Jin 

机构地区：[1]Beijing Key Laboratory of Cancer Invasion and Metastasis Research,Department of Anatomy,Histology and Embryology,School of Basic Medical Sciences,Advanced Innovation Center for Human Brain Protection,Capital Medical University,Beijing 100069,China [2]Institute of Neuroscience,The Second Affiliated Hospital of Soochow University,Suzhou 215004,China [3]School of Medicine,Ningbo University,Ningbo 315211,China [4]Zhejiang Provincial Key Laboratory of Pathophysiology,Ningbo 315211,China [5]Department of Pathology and Pathophysiology,Zhejiang University School of Medicine,Hangzhou 310058,China [6]Department of Physiology and Pathophysiology,Capital Medical University,Beijing 100069,China

出　　处：《Acta Pharmacologica Sinica》2023年第4期780-790,共11页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(81671145,81870973,81701316)。

摘　　要：Increasing evidence shows that smoking-obtained nicotine is indicated to improve cognition and mitigate certain symptoms of schizophrenia.In this study,we investigated whether chronic nicotine treatment alleviated MK-801-induced schizophrenia-like symptoms and cognitive impairment in mice.Mice were injected with MK-801(0.2 mg/kg,i.p.),and the behavioral deficits were assessed using prepulse inhibition(PPI)and T-maze tests.We showed that MK-801 caused cognitive impairment accompanied by increased expression of PDZ and LIM domain 5(Pdlim5),an adaptor protein that is critically associated with schizophrenia,in the prefrontal cortex(PFC).Pretreatment with nicotine(0.2 mg·kg^(−1)·d^(−1),s.c.,for 2 weeks)significantly ameliorated MK-801-induced schizophrenia-like symptoms and cognitive impairment by reversing the increased Pdlim5 expression levels in the PFC.In addition,pretreatment with nicotine prevented the MK-801-induced decrease in CREB-regulated transcription coactivator 1(CRTC1),a coactivator of CREB that plays an important role in cognition.Furthermore,MK-801 neither induced schizophrenia-like behaviors nor decreased CRTC1 levels in the PFC of Pdlim5^(−/−) mice.Overexpression of Pdlim5 in the PFC through intra-PFC infusion of an adreno-associated virus AAV-Pdlim5 induced significant schizophrenia-like symptoms and cognitive impairment.In conclusion,chronic nicotine treatment alleviates schizophrenia-induced memory deficits in mice by regulating Pdlim5 and CRTC1 expression in the PFC.

关 键 词：SCHIZOPHRENIA NICOTINE working memory Pdlim5 CRTC1 prefrontal cortex 

分 类 号：R285.5[医药卫生—中药学]