Feng Yu, Ma Xiaohui, Zong Xuemei, Jordan J Dedrick, Wu Celeste Yin-Chieh, Tesic Vesna, Lee Reggie Hui-Chao, Zhang Quanguang
Department of Neurology, Louisiana State University Health, 1501 Kings Highway, Shreveport, LA 71103, USA.
Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA.
Biomed Pharmacother. 2025 Apr;185:117916. doi: 10.1016/j.biopha.2025.117916. Epub 2025 Mar 9.
Neonatal hypoxia-ischemia (HI) results in gray and white matter injuries, leading to impairments in social behavior and severe neurological deficits. Clemastine treatment has demonstrated efficacy in alleviating behavioral deficits in various neurological disorders by improving myelin formation. It has been suggested that the medial prefrontal cortex (mPFC) and the striatum play a key role in human social behaviors. To test whether clemastine can mitigate sociability deficits by rescuing the myelin damage in these key brain areas, we administered clemastine orally for two weeks following HI insult in neonatal rats. We demonstrated that clemastine successfully ameliorated HI-induced social deficits during adolescence, attenuated hypomyelination and promoted oligodendrocyte maturation in the striatum and mPFC. We also observed that clementine reduced proliferation and apoptosis of oligodendrocyte progenitor cells (OPCs), decreased myelin debris induced by HI in the striatum, and was accompanied by microglia morphological changes in the striatum. Furthermore, our findings revealed a positive correlation between sociability and myelin formation in the striatum and mPFC. In conclusion, our data indicate that clemastine attenuates HI-induced sociability impairments during adolescence, potentially through its role in promoting myelin formation in the striatum and mPFC.
新生儿缺氧缺血（HI）会导致灰质和白质损伤，进而引发社会行为障碍和严重的神经功能缺损。氯马斯汀治疗已被证明可通过改善髓鞘形成来缓解各种神经疾病中的行为缺陷。有人提出，内侧前额叶皮质（mPFC）和纹状体在人类社会行为中起关键作用。为了测试氯马斯汀是否能通过挽救这些关键脑区的髓鞘损伤来减轻社交能力缺陷，我们在新生大鼠HI损伤后口服氯马斯汀两周。我们证明，氯马斯汀成功改善了青春期HI诱导的社交缺陷，减轻了髓鞘形成不足，并促进了纹状体和mPFC中少突胶质细胞的成熟。我们还观察到，氯马斯汀减少了少突胶质前体细胞（OPC）的增殖和凋亡，减少了HI诱导的纹状体中的髓鞘碎片，并伴有纹状体中微胶质细胞形态的变化。此外，我们的研究结果揭示了纹状体和mPFC中社交能力与髓鞘形成之间的正相关关系。总之，我们的数据表明，氯马斯汀可能通过促进纹状体和mPFC中的髓鞘形成，减轻青春期HI诱导的社交障碍。
