第三军医大学Yuxin Wang等研究人员合作发现，氟西汀能挽救PTSD小鼠模型中的过度髓鞘形成和心理行为。相关论文于2024年7月16日在线发表在《神经科学通报》杂志上。

研究人员采用了一种限制应激诱导的创伤后应激障碍（PTSD）小鼠模型，发现PTSD相关的神经精神症状伴随着后顶叶皮层和海马中的髓鞘增加。氟西汀，而不是利培酮或舍曲林，对神经心理行为和髓鞘异常有更显著的改善作用。

进一步的机制实验表明，氟西汀可以通过上调Wnt信号直接干扰少突胶质细胞的分化。这些数据表明PTSD与异常髓鞘形成之间存在相关性，提示少突胶质细胞谱系可能是PTSD治疗的一个靶点。

研究人员表示，PTSD是一种以创伤体验记忆为特征的复杂精神障碍。尽管目前的一线治疗与临床症状的显著减轻有关，但仍有大量患者保留相当多的残余症状，这表明需要进一步阐明病理机制。最近的研究报道，新形成的髓鞘可以影响神经回路功能，并参与恐惧记忆的保持。然而，其在PTSD中的作用尚待阐明。

附：英文原文

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

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

Issue&Volume: 2024-07-16

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.

DOI: 10.1007/s12264-024-01249-4

Source: https://link.springer.com/article/10.1007/s12264-024-01249-4