小柯机器人

南京大学Chao Yan、Dijun Chen、Zhang-Peng Chen和南京大学医学院Xiangyu Liu共同合作，近期取得重要工作进展。他们研究发现脂质积聚的反应性星形胶质细胞能促进癫痫的疾病进展。相关研究成果2023年3月20日在线发表于《自然—神经科学》杂志上。

据介绍，反应性星形胶质细胞在神经系统疾病中发挥着重要作用，但其在癫痫中的分子和功能表型尚不清楚。

研究人员发现，在颞叶癫痫（TLE）患者和癫痫小鼠模型中，星形胶质细胞中过度的脂质积聚导致脂质积聚反应性星形胶质细胞（LARA）的形成，这是一种新的反应性星形胶质细胞亚型，其特征是APOE表达升高。APOE基因敲除可以抑制癫痫小鼠LARA的形成和癫痫发作活动。TLE患者的单核RNA测序证实了具有独特分子特征的LARA亚群的存在。对癫痫小鼠模型和人脑切片的功能研究表明，LARA促进神经元过度活跃和疾病进展。

总之，这一研究表明，通过脂质转运和代谢干预靶向LARA可以为耐药TLE提供新的治疗选择。

附：英文原文

Title: Lipid-accumulated reactive astrocytes promote disease progression in epilepsy

Author: Chen, Zhang-Peng, Wang, Suji, Zhao, Xiansen, Fang, Wen, Wang, Zhengge, Ye, Haojie, Wang, Meng-Ju, Ke, Ling, Huang, Tengfei, Lv, Pin, Jiang, Xiaohong, Zhang, Qipeng, Li, Liang, Xie, Shu-Tao, Zhu, Jing-Ning, Hang, Chunhua, Chen, Dijun, Liu, Xiangyu, Yan, Chao

Issue&Volume: 2023-03-20

Abstract: Reactive astrocytes play an important role in neurological diseases, but their molecular and functional phenotypes in epilepsy are unclear. Here, we show that in patients with temporal lobe epilepsy (TLE) and mouse models of epilepsy, excessive lipid accumulation in astrocytes leads to the formation of lipid-accumulated reactive astrocytes (LARAs), a new reactive astrocyte subtype characterized by elevated APOE expression. Genetic knockout of APOE inhibited LARA formation and seizure activities in epileptic mice. Single-nucleus RNA sequencing in TLE patients confirmed the existence of a LARA subpopulation with a distinct molecular signature. Functional studies in epilepsy mouse models and human brain slices showed that LARAs promote neuronal hyperactivity and disease progression. Targeting LARAs by intervention with lipid transport and metabolism could thus provide new therapeutic options for drug-resistant TLE.

DOI: 10.1038/s41593-023-01288-6

Source: https://www.nature.com/articles/s41593-023-01288-6

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex