Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice

doi:10.3390/biomedicines11092483

	Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice
	Gao, Yining 1; Li, Hongxia 1; Luo, Huoqing2 ; Ni, You 1; Feng, Yifan2 ; He, Lu 1; Zhou, Qinming 1; Hu, Ji2,3 ; Chen, Sheng 1,3
	2023-09-01
发表期刊	BIOMEDICINES
EISSN	2227-9059
卷号	11 期号:9
发表状态	已发表
DOI	10.3390/biomedicines11092483
摘要	Background: Anti-IgLON5 disease is a rare autoimmune disease of the central nervous system. It typically manifests as a chronic condition, characterized by cognitive impairments, movement disorders, and sleep disorders. The mechanisms underlying movement disorders in this disease remain poorly understood due to a lack of research. Furthermore, this disease exhibits both neuroimmune and neurodegenerative characteristics. The objective of this study is to explore the underlying mechanisms of movement disorders caused by anti-IgLON5 antibodies for the first time. Methods: Antibodies were purified from the serum of a confirmed patient of anti-IgLON5 disease. The passive transfer animal models were employed, where antibodies were continuously injected into the substantia nigra pars compacta (SNc) of the mouse midbrain using stereotactic injection to explore the mechanism of movement disorder. The effects of anti-IgLON5 antibodies on dopaminergic neurons in the SNc and neurodegeneration were examined through immunohistochemistry. Changes in neurotransmitter levels in the basal ganglia were assessed using high-performance liquid chromatography. Additionally, RNA-seq was employed to identify the differentially expressed genes associated with the short-term and long-term effects of anti-IgLON5 antibody on the SNc. Results: Mice injected with anti-IgLON5 antibodies in the SNc exhibited persistent movement impairments for up to 3 months. One week after antibody injection, the number of TH neurons significantly decreased compared to the control group, accompanied by reduced projection fibers in the basal ganglia and decreased dopamine levels. After 3 months of antibody injection, an increase in phosphorylated Tau was observed in the SNc of the midbrain. Additionally, long-term sustained activation of microglia was detected in the SNc. The differentially expressed genes of long-term effects of IgLON5 antibodies were different from their short-term effects on the SNc. Conclusion: Purified serum IgG from a patient with anti-IgLON5 antibodies can cause long-term movement disorder in mice. The movement disorders appear to be linked to the impaired dopaminergic pathway, and the increased p-Tau showed neurodegenerative changes induced by the anti-IgLON5 antibody.
关键词	anti-IgLON5 disease movement disorders neuropathology dopaminergic pathways substantia nigra pars compacta
URL	查看原文
收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Research & Experimental Medicine ; Pharmacology & Pharmacy
WOS类目	Biochemistry & Molecular Biology ; Medicine, Research & Experimental ; Pharmacology & Pharmacy
WOS记录号	WOS:001073744500001
出版者	MDPI
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/337719
专题	生命科学与技术学院生命科学与技术学院_PI研究组_胡霁组生命科学与技术学院_博士生
通讯作者	Hu, Ji; Chen, Sheng
作者单位	1.Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Neurol, Shanghai 200023, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226007, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Gao, Yining,Li, Hongxia,Luo, Huoqing,et al. Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice[J]. BIOMEDICINES,2023,11(9).
APA	Gao, Yining.,Li, Hongxia.,Luo, Huoqing.,Ni, You.,Feng, Yifan.,...&Chen, Sheng.(2023).Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice.BIOMEDICINES,11(9).
MLA	Gao, Yining,et al."Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice".BIOMEDICINES 11.9(2023).