Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder  

作　　者：Man Chen Yun‑Hui Chu Wen‑Xiang Yu Yun‑Fan You Yue Tang Xiao‑Wei Pang Hang Zhang Ke Shang Gang Deng Luo‑Qi Zhou Sheng Yang Wei Wang Jun Xiao Dai‑Shi Tian Chuan Qin 

机构地区：[1]Department of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Hubei Key Laboratory of Neural Injury and Functional Reconstruction,Huazhong University of Science and Technology,Wuhan 430030,China [3]Department of Neurology,Hainan General Hospital,Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,China

出　　处：《Neuroscience Bulletin》2024年第8期1104-1114,共11页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82371404,82271341,82071380,and 81873743);the Knowledge Innovation Program of Wuhan Shuguang Project(2022020801020454);the Tongji Hospital Foundation for Excellent Young Scientists(2020YQ06).

摘　　要：Neuromyelitis optica spectrum disorder(NMOSD)is an autoimmune inflammatory demyelinating disease of the central nervous system(CNS)accompanied by blood-brain barrier(BBB)disruption.Dysfunction in microglial lipid metabolism is believed to be closely associated with the neuropathology of NMOSD.However,there is limited evidence on the functional relevance of circulating lipids in CNS demyelination,cellular metabolism,and microglial function.Here,we found that serum low-density lipoprotein(LDL)was positively correlated with markers of neurological damage in NMOSD patients.In addition,we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB,directly activating microglia.This activation leads to excessive phagocytosis of myelin debris,inhibition of lipid metabolism,and increased glycolysis,ultimately exacerbating myelin damage.We also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in NMOSD.These findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage,highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.

关 键 词：Neuromyelitis optica spectrum disorder Low-density lipoprotein MICROGLIA 

分 类 号：R745[医药卫生—神经病学与精神病学]