Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model  

作　　者：Chenrui Yin Kefei Luo Xinyue Zhu Ronghang Zheng Yu Wang Guangdan Yu Xiaorui Wang Fei She Xiaoying Chen Tao Li Jingfei Chen Baduojie Bian Yixun Su Jianqin Niu Yuxin Wang 

机构地区：[1]Department of Histology and Embryology,Third Military Medical University,Chongqing 400038,China [2]Department of Respiratory Diseases,Central Medical Branch of PLA General Hospital,Beijing 100853,China [3]China Astronaut Research and Training Center,Beijing 100094,China [4]Department of Emergency,the Fourth Medical Center of the Chinese PLA General Hospital,Beijing 100142,China [5]Army 953 Hospital,Shigatse Branch of Xinqiao Hospital,Third Military Medical University(Army Medical University),Shigatse 857000,China [6]Research Centre,Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen 518107,China

出　　处：《Neuroscience Bulletin》2024年第8期1037-1052,共16页神经科学通报（英文版）

基　　金：supported by grants from the National Nature Science Foundation of China(32271034,32070964,82301703,32300791,and 81901378);Science and Technology Innovation Enhancement Project of Army Medical University(2022XQN40);National Key Research and Development Program of China(2021ZD0201703);Chongqing Natural Science Fund for Distinguished Young Scholars(CSTB2023NSCQ-JQX0030);Undergraduate Research Cultivation Project of Army Medical University(2020XBK16);Guangdong Basic and Applied Basic Research Foundation(2021A1515110268 and 2023A1515010651);Shenzhen Fundamental Research Program(RCBS20210706092411028 and JCYJ20210324121214039).

摘　　要：Posttraumatic stress disorder(PTSD)is a complex mental disorder notable for traumatic experience memory.Although current first-line treatments are linked with clinically important symptom reduction,a large proportion of patients retained to experience considerable residual symptoms,indicating pathogenic mechanism should be illustrated further.Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation.However,its role in PTSD remains to be elucidated.In this study,we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus.Fluoxetine,but not risperidone or sertraline,has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities.Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling.Our data demonstrated the correlation between PTSD and abnormal myelination,suggesting that the oligodendroglial lineage could be a target for PTSD treatment.

关 键 词：PTSD Fear memory MYELINATION Oligodendroglial differentiation FLUOXETINE Wnt signaling 

分 类 号：R749[医药卫生—神经病学与精神病学]