Crosstalk between autophagy and apoptosis regulates cerebral cortex and cerebellum neurodegeneration induced by cadmium in swine via the PI3K/ AKT/AMPK pathway

Cadmium (Cd) chloride, a ubiquitous environmental pollutant, impairs nerve function and is associated with neurodegeneration. The aim of this study was to investigate the molecular mechanism of nerve damage caused by Cd exposure in swine. Six-week-old weaned pigs were exposed to CdCl2 (20 mg/kg) for 40 days. Subsequently, real-time quantitative PCR (qRT-PCR) and western blotting (WB) were applied to validate the genes. Our results showed that Cd exposure downregulated protein expression of p-PI3K/PI3K, p-AKT/AKT, and mTOR in the cerebral cortex and cerebellum, whereas protein expression of AMPK, Beclin-1, LC3-II/LC3-I, ATG5 and ATG7 was upregulated. Moreover, we found that Cd exposure stimulated increased mRNA and protein levels of Caspase-3, Caspase-9, and Bax and decreased Bcl-2 levels to initiate apoptosis. In addition, our results revealed that Cd exposure destroyed the nerve cell structure in the cerebral cortex and reduced the number of nerve cells in the cerebellum. The severity of cerebellar injuries was higher than that in the cerebral cortex. Overall, we found that Cd led to PI3K/AKT inhibition and AMPK activation to enhance autophagy and induce apoptosis. Our research paves a pathway for mining neurodegeneration in response to Cd exposure.

Automated summary

Exposure to Cd led to nerve damage in pigs through inhibition of the PI3K/AKT pathway, activation of AMPK to enhance autophagy, and induction of apoptosis. The study provides insights into neurodegeneration in response to Cd exposure.