The 28-day repeated arsenic exposure increases tau phosphorylation in the rat brain

• DOI: 10.1016/j.etap.2022.103974
• Publication Date: 2022-09-08T16:03:54Z
• Authors: Churaibhon Wisess...; Luksamee Worasutt...; Kanjanamas Maliphol; Watanyoo Nakarean...; Wanida Cholpraipi...; Sumontha Nookabkaew; Piyajit Watcharasit; Jutamaad Satayavivad
• Keywords: Cyclin-dependent kinase 5

Herein, we examined whether prolonged arsenic exposure altered tau phosphorylation in the brain of Sprague Dawley rats expressing endogenous wild-type tau. The results showed that daily intraperitoneal injections of 2.5 mg/kg BW sodium arsenite over 28 days caused arsenic accumulation in the rat brain. Interestingly, we found an increase in tau phosphorylation at the Tau 1 region (189-207) and S202 in the hippocampus, S404 in the cerebral cortex, and S396 and S404 in the cerebellum of arsenic-treated rats. Additionally, arsenic increased active ERK1/2 phosphorylation at T202/Y204 in the hippocampus, cerebral cortex, and cerebellum. Meanwhile, we detected increasing active JNK phosphorylation at T183/Y185 in the hippocampus and cerebellum. Moreover, p35, a neuron-specific activator of CDK5, was also elevated in the cerebellum of arsenic-treated rats, suggesting that CDK5 activity may be increased by arsenic. These results suggested that arsenic may induce tau phosphorylation through the activation of tau kinases, ERK1/2, JNK, and CDK5. Together, the findings from this study demonstrated that prolonged arsenic exposure is implicated in neurodegeneration by promoting tau phosphorylation in the rat brain and points toward a possible prevention strategy against neurodegeneration induced by environmental arsenic exposure.