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.

在这里，我们检查了长时间的砷暴露是否会改变表达内源性野生型 tau 的 Sprague Dawley 大鼠大脑中的 tau 磷酸化。结果表明，在 28 天内每天腹腔注射 2.5 mg/kg BW 亚砷酸钠会导致大鼠脑中的砷蓄积。有趣的是，我们发现经过砷处理的大鼠，Tau 1 区域 (189-207) 和海马中的 S202、大脑皮层中的 S404 以及小脑中的 S396 和 S404 中的 tau 磷酸化增加。此外，砷增加了海马、大脑皮层和小脑中 T202/Y204 处的活性 ERK1/2 磷酸化。同时，我们检测到海马和小脑中 T183/Y185 处的活性 JNK 磷酸化增加。此外，p35，一种 CDK5 的神经元特异性激活剂，在砷处理的大鼠的小脑中也升高，这表明 CDK5 活性可能因砷而增加。这些结果表明，砷可能通过激活 tau 激酶、ERK1/2、JNK 和 CDK5 来诱导 tau 磷酸化。总之，这项研究的结果表明，长时间的砷暴露通过促进大鼠大脑中的 tau 磷酸化与神经退行性变有关，并指出了一种可能的预防策略，以防止环境砷暴露引起的神经退行性变。