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The role of microglia activated by the deletion of immune checkpoint receptor CD200R1 gene in a mouse model of Parkinson's disease

GUO Jia-Li^1,2, HUANG Tao-Ying^1,2, ZHANG Zhen^1,2, NIU Kun^1,2, GONGBIKAI Xarbat^1,2, GONG Xiao-Li^2,3, WANG Xiao-Min^2,3, ZHANG Ting^1,2,*

¹Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China；²Key Laboratory of Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China；³Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

Abstract

The study aimed to investigate the effect of the CD200R1 gene deletion on microglia activation and nigrostriatal dopamine neuron loss in the Parkinson's disease (PD) process. The CRISPR-Cas9 technology was applied to construct the CD200R1^-/- mice. The primary microglia cells of wild-type and CD200R1^-/- mice were cultured and treated with bacterial lipopolysaccharide (LPS). Microglia phagocytosis level was assessed by a fluorescent microsphere phagocytosis assay. PD mouse model was prepared by nigral stereotaxic injection of recombinant adeno-associated virus vector carrying human α-synuclein (α-syn). The changes in the motor behavior of the mice with both genotypes were evaluated by cylinder test, open field test, and rotarod test. Immunohistochemical staining was used to assess the loss of dopamine neurons in substantia nigra. Immunofluorescence staining was used to detect the expression level of CD68 (a key molecule involved in phagocytosis) in microglia. The results showed that CD200R1 deletion markedly enhanced LPS-induced phagocytosis in vitro by the microglial cells. In the mouse model of PD, CD200R1 deletion exacerbated motor behavior impairment and dopamine neuron loss in substantia nigra. Fluorescence intensity analysis results revealed a significant increase in CD68 expression in microglia located in the substantia nigra of CD200R1^-/- mice. The above results suggest that CD200R1 deletion may further activates microglia by promoting microglial phagocytosis, leading to increased loss of the nigrostriatal dopamine neurons in the PD model mice. Therefore, targeting CD200R1 could potentially serve as a novel therapeutic target for the treatment of early-stage PD.

Key words: CD200R1; microglia; phagocytosis; Parkinson's disease

Received: 　　Accepted:

Corresponding author: 张婷　　E-mail:

DOI: 10.13294/j.aps.2025.0018

Citing This Article：

GUO Jia-Li, HUANG Tao-Ying, ZHANG Zhen, NIU Kun, GONGBIKAI Xarbat, GONG Xiao-Li, WANG Xiao-Min, ZHANG Ting. The role of microglia activated by the deletion of immune checkpoint receptor CD200R1 gene in a mouse model of Parkinson's disease. Acta Physiol Sin 2025; 77 (1): 13-24 (in Chinese with English abstract).