Perinatal arsenic exposure-induced sustained microglial activation leads to impaired cognitive response in BALB/c...

Arsenic is infamous for its adverse health effects worldwide. It is known to induce cognitive impairment in experimental model animals and children in the arsenic-affected area. Although the effect of arsenic on neuronal health is well studied, but the involvement of the brain immune component, microglia, has not been well explored. The present study is focused on examining the role of microglia in arsenic-induced cognitive impairment. We have used balb/c mice for the study. Pregnant dams were gavaged with sodium arsenite (0.38 mg/kg body weight) from gestational day 5 (GD5) till postnatal day 22 (PND22). Mice were sacrificed on PND 7, 14, 22 and isolated brains were used for various assays. The study reveals that perinatal arsenic exposure keeps the microglia activated and skews them towards the M1 phenotype. Increased microglial proliferation, ROS, NO, higher levels of proinflammatory cytokines and chemokines were observed in the arsenic exposed group. Enhanced phagocytosis and phagocytic receptor TREM2, along with decreased expression of SNAP25 and PSD95, were correlated for enhanced neuronal pruning leading to impaired learning and memory response. Taken together, the study reveals an association between arsenic exposure and altered cognitive response where enhanced neuronal pruning by arsenic-activated microglia plays an important role in developing mice.