The effects of copper sulfate on the structure and function of the rat cerebellum: A stereological and behavioral study

Copper (Cu) is a vital trace element that acts as a cofactor of proteins and enzymes in many molecular pathways including the central nervous system. The accumulation or deficiency of copper could alter neuronal function and lead to neuronal degeneration and brain dysfunction. Intake of high levels of copper can also cause copper toxicosis that affects the brain structure and function. Despite clinical and experimental data indicating the association between abnormal copper homeostasis and brain dysfunction, the effects of copper on cerebellum have remained poorly understood. Hence, this study aimed to evaluate the effects of copper sulfate on the cerebellum via stereological and behavioral methods in rats. Male rats (Sprague-Dawley) were divided to three groups. The rats in the control group orally received distilled water, while those in the Cu groups received 1 mM (159 mg/L) or 8 mM (1272 mg/L) copper sulfate by oral gavage solved in distilled water daily for 4 weeks. Then, the rotarod performance test was recorded and the cerebellum was prepared for stereological assessments. The Cu-administered rats (1 and 8 mM) exhibited a significant reduction in the total volumes of the cerebellum structures. The total number of the cells in the cerebellar cortex and deep cerebellar nuclei were significantly decreased via Cu in a dose-dependent manner. Furthermore, the length of nerve fibers and the number of spines per nerve fiber decreased significantly in the Cu groups. These changes were correlated to the animals' motor performance impairment in the rotarod test. The findings suggested that copper toxicity induced motor performance impairments in the rats, which could be attributed to its deleterious effects on the cerebellum structure.