CD200Fc attenuates LPS-induced neuroinflammation and motor deficits via modulation of microglial activation and autophagy

Abstract

This study investigated the therapeutic potential of CD200Fc in a mouse model of chronic neuroinflammation induced by intraperitoneal lipopolysaccharide (LPS) injections administered every other day for four weeks. Wild-type mice (Male mice aged 8 weeks) were divided into four groups: WT + PBS, WT + LPS, LPS + PBS, and LPS+CD200Fc ( n  = 16 per group). CD200Fc (4 µg per mouse, prepared at 2 µg/µL) was administered via intracerebroventricular stereotaxic injection at an infusion rate of 0.2µL/min, and intraperitoneal LPS injection was performed continuously within two weeks before and after treatment. The motor function of mice was assessed one week after model establishment using open-field, rotarod, and pole tests. Neuroinflammatory markers, microglial activation, autophagy function, and neuronal damage were evaluated via immunofluorescence and Western blot. The WT + LPS group exhibited significant motor dysfunction compared to WT + PBS controls, along with elevated levels of neuroinflammation-related proteins (including IL-18, IL-1β, and NLRP3) and the microglial activation marker CD68. These changes were accompanied by autophagic dysfunction and dopaminergic neuron loss. In contrast, the LPS+CD200Fc group showed notable improvements in motor function, reduced NLRP3 inflammasome activation, attenuated neuroinflammation, and restoration of autophagy. Dopaminergic neuronal damage was also significantly alleviated. These results indicate that CD200Fc significantly ameliorates LPS-induced neuroinflammation and motor dysfunction by suppressing microglial activation and restoring autophagic function. This supports further investigation into CD200Fc as a promising candidate for treating neuroinflammatory disorders of the central nervous system (CNS).