医学创新论坛第18期

Time：2:00 PM, March 22, 2024 (Friday)

Location: Room 1322, North Tower, Basic Research Building, Capital Medical University (首都医科大学基础科研楼北楼1322会议室)

Host: Lin Mei

     Chinese Institutes for Medical Research, Beijing

Speaker: Xiaoping Tong (童小萍) Investigator

Shanghai Jiao Tong University School of Medicine

Title: New strategy of targeting Kir4.1 channels in the repair of multiple sclerosis

Abstract:

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Axonal demyelination is considered to be the main factor leading to permanent neurological dysfunction in MS patients. Up to now, many believe autoimmune pathogenesis plays a key role in MS, but its target remains elusive. Here, we found that impaired Kir4.1 channels in spinal cord initially occurred in NG2 glia but not astrocytes in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Through thermal shift assay screening, we identified a small molecular compound HT001 to be an activator of Kir4.1 channel. Treating EAE mice with HT001, we found that this molecule protected EAE-induced demyelination in spinal cord and ultimately improved motor functions in a series of behavioral tests of EAE mice. Our finding highlights a key role of Kir4.1 channel in MS pathogenesis and pharmacological activation of Kir4.1 channel by HT001 illustrates a potential neuroprotective strategy for functional brain recovery in demyelinating diseases.

Selected publications:

Hong X, Jian Y, Ding S, Zhou J, Zheng X, Zhang H, Zhou B, Zhuang C, Wan, J*, Tong X*. Kir4.1 channel activation in NG2 glia contributes to remyelination in ischemic stroke. EBioMedicine. 2023, 87, 104406.

Zhang X, Liu Y, Hong X, Li X, Meshul CK, Moore C, Yang Y, Han Y, Li W, Xin Q, Lou H, Duan S, Xu T, Tong X*. NG2 glia-derived GABA release tunes inhibitory synapses and contributes to stress-induced anxiety. Nature Communications. 2021, 12(1): 5740.

Zhou B, Zhu Z, Ransom BR*, Tong X*. Oligodendrocyte lineage cells and depression. Molecular Psychiatry. 2021, 26(1): 103~117.

个人简介：童小萍，研究员，博士生导师。上海市高校特聘教授“东方学者”，上海市“浦江人才”计划A类获得者，国际知名学术期刊GLIA编委。2009年博士毕业于中国科学院神经科学研究所，2009-2014年先后在美国加州大学洛杉矶分校生理系、神经生物系担任博士后和项目科学家，并于2014年获得美国UCLA“杰出博士后”校长奖。2014年10月加入上海交通大学医学院基础医学院，任“胶质细胞的生物学功能与脑疾病”研究组组长。主要从事胶质细胞调控神经环路以及在神经系统疾病的发病机理研究。相关研究发表于Nature Neuroscience、Nature Communications、Molecular Psychiatry、EBioMedicine等神经科学领域国际专业权威杂志。