Microglial depletion rescues spatial memory impairment caused by LPS administration in adult mice
Tao Zong,
Na Li,
Fubing Han,
Junru Liu,
Mingru Deng,
Vincent Li,
Meng Zhang,
Yu Zhou,
Ming Yu
Affiliations
Tao Zong
Affiliated Qingdao Third People’s Hospital, Department of Otorhinolaryngology Head and Neck, Qingdao University, Qingdao, China
Na Li
Institute of Brain Sciences and Related Disorders, Qingdao University, Qingdao, China, China
Fubing Han
Institute of Brain Sciences and Related Disorders, Qingdao University, Qingdao, China, China
Junru Liu
Department of Neurology, Affiliated Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao, China, China
Mingru Deng
Institute of Brain Sciences and Related Disorders, Qingdao University, Qingdao, China, China
Vincent Li
Beverly Hills High School, Unaffiliated, Beverly Hills, California, United States
Meng Zhang
Institute of Brain Sciences and Related Disorders, Qingdao University, Qingdao, China, China
Yu Zhou
Affiliated Qingdao Third People’s Hospital, Department of Otorhinolaryngology Head and Neck, Qingdao University, Qingdao, China
Ming Yu
Department of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China
Recent studies have highlighted the importance of microglia, the resident macrophages in the brain, in regulating cognitive functions such as learning and memory in both healthy and diseased states. However, there are conflicting results and the underlying mechanisms are not fully understood. In this study, we examined the effect of depleting adult microglia on spatial learning and memory under both physiological conditions and lipopolysaccharide (LPS)-induced neuroinflammation. Our results revealed that microglial depletion by PLX5622 caused mild spatial memory impairment in mice under physiological conditions; however, it prevented memory deficits induced by systemic LPS insult. Inactivating microglia through minocycline administration replicated the protective effect of microglial depletion on LPS-induced memory impairment. Furthermore, our study showed that PLX5622 treatment suppressed LPS-induced neuroinflammation, microglial activation, and synaptic dysfunction. These results strengthen the evidence for the involvement of microglial immunoactivation in LPS-induced synaptic and cognitive malfunctions. They also suggest that targeting microglia may be a potential approach to treating neuroinflammation-associated cognitive dysfunction seen in neurodegenerative diseases.
