海马少突胶质细胞调节苔藓纤维发育参与癫痫反应，这一成果由杭州师范大学赵晓峰课题组经过不懈努力而取得。该研究于2025年7月17日发表于国际一流学术期刊《神经科学通报》杂志上。

在本研究中，研究团队发现Myrf-CKO小鼠的OL成熟缺陷导致自发性癫痫发生并导致死亡。为了进一步研究OL发育与癫痫之间的关系，研究小组检测了Adamts4 KO母主题系，该系在海马中具有轻度OL分化表型。结果，突变海马的分化缺陷降低了髓磷脂相关糖蛋白的表达，并减弱了其对磷酸化原肌球蛋白相关激酶B去磷酸化的抑制作用，这与青少年海马苔藓纤维发育迟缓和成年后更易发生癫痫有关。更重要的是，通过口服clemastine增强分化，可以挽救出生后早期有缺陷的苔藓纤维发育，并减轻成人癫痫的易感性。总之，这些结果强烈表明，海马的OL分化缺陷可能有助于成人癫痫的易感性。

据了解，虽然已知少突胶质细胞（OLs）在神经元轴突周围形成髓鞘，用于动作电位的跳跃传导，但最近的研究表明，OLs也调节神经元的功能和可塑性。

附：英文原文

Title: Hippocampal Oligodendrocytes Regulate Mossy Fiber Development Involved in Epileptic Responses

Author: Jiang, Chunxia, Hu, Yunan, Zhang, Feng, Qiu, Mengsheng, Zhao, Xiaofeng

Issue&Volume: 2025-07-17

Abstract: Although oligodendrocytes (OLs) are known to form the myelin sheath around neuronal axons for the saltatory conduction of action potentials, recent studies have suggested that OLs also modulate neuronal function and plasticity. In the present study, we found that OL maturation deficiency in Myrf-CKO mice caused spontaneous epileptogenesis and resulted in death. To further investigate the association between OL development and epilepsy, we examined the Adamts4 KO mouse line, which has a mild OL differentiation phenotype in the hippocampus. As a result, the differentiation defect in the mutant hippocampus reduced the expression of myelin-associated glycoprotein and lessened its inhibition of the dephosphorylation of phosphorylated tropomyosin-related kinase B, which is associated with retarded adolescent hippocampal mossy fiber development and higher susceptibility to epileptogenesis in adulthood. More importantly, enhancing differentiation by orally administered clemastine rescues the defective mossy fiber development in the early postnatal period and attenuates epilepsy susceptibility in adults. Together, these results strongly suggest that an OL differentiation defect in the hippocampus may contribute to susceptibility to epilepsy in adults.

DOI: 10.1007/s12264-025-01452-x

Source: https://link.springer.com/article/10.1007/s12264-025-01452-x