BACKGROUND: Prolonged lithium therapy in psychiatric disorders may be complicated by multi-organ dysfunction, particularly in the nervous system. Toxicity to the cerebellum is one of these, which, while uncommon, inevitably emerges negatively and permanently. Selenium is a trace element regarded as one of the critical antioxidants. Numerous investigations have validated selenium's neuroprotective properties against various neurotoxic medications. The degree of affliction of the nerve cells is assessed using GFAP, a marker of astrocytosis
Caspase-3, a marker of apoptosis
and klotho, a marker of anti-aging. AIM OF THE STUDY: This study is designed to investigate the cerebellar structural and functional changes in lithium-treated rats and the postulated neuroprotective role of selenium. METHODOLOGY: A total of 24 adult male albino rats were divided into 4 groups: control, selenium (1 mg/kg in water solution by gavage daily), lithium (by intraperitoneal injection of 25 mg/kg lithium carbonate dissolved in 0.9 % NaCL twice daily for 4 weeks), and lithium-selenium group. Motor coordination was evaluated using the rotarod test. Cerebellar malonaldehyde (MDA) and reduced glutathione (GSH) were measured, and histopathological examination and immunohistochemical expression of Klotho, GFAP, and Caspase 3 were evaluated. RESULTS: The lithium-treated group exhibited reduced latency on the rotarod test, elevated oxidative stress indicators, and an altered cerebellar structure in HE and cresyl violet-stained sections. Moreover, there was a diminished Klotho expression and increased levels of both caspase-3 and GFAP expression. Selenium administration reduced latency time, diminished oxidative stress markers, mitigated lithium-induced cerebellar alterations, increased Klotho expression, and lowered the expression of caspase-3 and GFAP. CONCLUSION: Lithium exposure causes alterations in the cerebellar cortical structure in albino rats. Selenium protected the cerebellar cortex from such changes by enhancing Klotho expression, diminishing oxidative stress, and reducing apoptosis.