Cellular Mechanisms Involved in Cadmium-Mediated Cerebellar Toxicity.

Abstract

Cadmium (Cd) is a widespread environmental pollutant with well-documented neurotoxic effects. The cerebellum, a key region for motor coordination, appears particularly vulnerable to Cd-induced damage. Numerous recent studies have investigated Cd-mediated cerebellar toxicity, yet an integrated interpretation of these findings remains limited.Here, we summarize current knowledge on histopathological and molecular alterations in the cerebellum following Cd exposure. Cadmium disrupts redox balance by generating reactive oxygen species (ROS) and depleting endogenous antioxidant defenses, including superoxide dismutase (SOD) and glutathione peroxidase (GPx). It also interferes with metal homeostasis, promoting accumulation of copper and manganese while reducing levels of zinc, selenium, and iron. Cd alters the expression of metal transporters and impairs synthesis of metallothioneins and heat shock proteins.Histologically, Cd exposure affects all three layers of the cerebellar cortex and leads to Purkinje and granular cell loss. Molecular markers of apoptosis (e.g., Bax, caspases, TUNEL-positive nuclei) and necrosis (e.g., RIPK1/3) are commonly elevated. Additionally, Cd impairs key signaling pathways such as PI3K/AKT and Sonic Hedgehog (Shh), and reduces neurotransmitter levels.Experimental evidence from multiple animal models (rats, piglets, chickens, etc.) consistently demonstrates cerebellar accumulation of Cd and associated pathological changes. Importantly, several interventions-including nano-selenium, soy-based diets, and natural antioxidants-have shown protective effects against Cd-induced cerebellar toxicity.