法国里昂第一大学Christophe Heinrich小组发现，将反应性胶质细胞重编程为中间神经元可减少中颞叶癫痫小鼠模型的慢性发作活动。相关论文于2021年9月29日在线发表于国际学术期刊《细胞—干细胞》。

研究人员表示，将驻脑胶质细胞重新编程为临床相关的诱导神经元（iN）是一种新兴的战略，能够取代失去的神经元和恢复失去的大脑功能。现在的一个基本问题是iN是否能促进病理情况下的功能恢复。

研究人员在耐药的中颞叶癫痫（MTLE）的背景下解决了这个问题，该病与海马发作和海马GABA能中间神经元的退化有关。利用MTLE小鼠模型，研究人员表明，逆转录病毒驱动的Ascl1和Dlx2在原位的反应性海马胶质细胞或移植到癫痫海马的皮层星形胶质细胞中的表达，会导致有效地重新编程为iN，表现出神经元的特征。这些诱导的中间神经元在功能上融入癫痫网络，并在齿状颗粒细胞上建立GABA能突触。

带有GABA能iN的MTLE小鼠显示出自发复发性海马发作的数量和累积时间都明显减少。因此，胶质细胞到神经元的重编程是一种潜在的疾病调节策略，可以减少治疗性癫痫的发作。

附：英文原文

Title: Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy

Author: Célia Lentini, Marie d’Orange, Nicolás Marichal, Marie-Madeleine Trottmann, Rory Vignoles, Louis Foucault, Charlotte Verrier, Céline Massera, Olivier Raineteau, Karl-Klaus Conzelmann, Sylvie Rival-Gervier, Antoine Depaulis, Benedikt Berninger, Christophe Heinrich

Issue&Volume: 2021-09-29

Abstract: Reprogramming brain-resident glial cells into clinically relevant induced neurons (iNs) is an emerging strategy toward replacing lost neurons and restoring lost brain functions. A fundamental question is now whether iNs can promote functional recovery in pathological contexts. We addressed this question in the context of therapy-resistant mesial temporal lobe epilepsy (MTLE), which is associated with hippocampal seizures and degeneration of hippocampal GABAergic interneurons. Using a MTLE mouse model, we show that retrovirus-driven expression of Ascl1 and Dlx2 in reactive hippocampal glia in situ, or in cortical astroglia grafted in the epileptic hippocampus, causes efficient reprogramming into iNs exhibiting hallmarks of interneurons. These induced interneurons functionally integrate into epileptic networks and establish GABAergic synapses onto dentate granule cells. MTLE mice with GABAergic iNs show a significant reduction in both the number and cumulative duration of spontaneous recurrent hippocampal seizures. Thus glia-to-neuron reprogramming is a potential disease-modifying strategy to reduce seizures in therapy-resistant epilepsy.

DOI: 10.1016/j.stem.2021.09.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00378-7