Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model
Chenrui Yin1 · Kefei Luo1 · Xinyue Zhu1 · Ronghang Zheng1 · Yu Wang2 · Guangdan Yu3 · Xiaorui Wang1 · Fei She4 · Xiaoying Chen1 · Tao Li1 · Jingfei Chen1 · Baduojie Bian5 · Yixun Su6 · Jianqin Niu1 · Yuxin Wang1,51 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 Afliated Hospital of Sun Yat-sen University, Shenzhen 518107, China
Abstract
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.
Keywords
PTSD; Fear memory; Myelination; Oligodendroglial diferentiation; Fluoxetine; Wnt signaling
