부산대학교 도서관

Inwardly rectifying Kir4.1 channels are specifically expressed in astrocytes and involved in the pathogenesis of various brain diseases, including depression, epilepsy, and Alzheimer’s disease (Int. J. Mol. Sci., 22, 10236, 2021). Previous studies reported that repeated administration of lipopolysaccharide (LPS) induced neuroinflammation and cognitive impairment in mice (Sci. Rep., 9, 5790, 2019). To explore the role of astrocytic Kir4.1 channels in development of neuroinflammatory cognitive impairment, we evaluated the effect of the Kir4.1 blocker, quinacrine, on LPS-induced cognitive impairment. Treatment of mice with LPS (0.4 mg/kg, i.p.) for 7 days significantly impaired cognitive function in the novel object recognition test. In addition, immunohistochemical analysis revealed that the LPS treatment significantly increased GFAP expression in the hippocampus. On the other hand, administration of quinacrine (30 mg/kg, s.c.) significantly improved LPS-induced cognitive impairment and also reversed the elevation of GFAP expression by LPS. These results suggest that inhibition of astrocytic Kir4.1 channels is effective for the treatment of neuroinflammatory cognitive impairment.