The neuroprotective effect of simvastatin on the cerebellum of experimentally-induced diabetic rats through klotho upregulation: An immunohistochemical study

Background: Diabetes mellitus is a multifactorial metabolic disorder that is complicated by multi-organ dysfunction including CNS. Klotho is an anti-aging protein expressed in Purkinje cells of the cerebellum. Klotho protects against the development of several neurodegenerative diseases. Simvastatin is a lipophilic statin that can enhance klotho expression. Aim of the study: This study was designed to investigate cerebellar structural changes in diabetes, klotho expression in the cerebellum of diabetic rats and the neuroprotective effect of simvastatin. Materials & methods: 24 adult albino rats were divided into 4 groups; control, simvastatin, diabetic (induced by single intraperitoneal injection of STZ 45 mg/kg) and diabetic treated by simvastatin (10 mg/kg once daily) after confirmation of diabetes. Rotarod test was performed for evaluation of motor coordination. Blood glucose and insulin levels were estimated for confirmation of diabetes. Reduced glutathione (GSH) and malonaldehyde (MDA) in cerebellar tissues were evaluated. The cerebellar samples were prepared for histological and immunohistochemical staining. Results: The latency time on the rotarod was reduced in diabetic rats. Cerebellar structure was disturbed in diabetic group. Oxidative stress was evidenced by increased MDA and reduced GSH. Klotho expression was downregulated and caspase-3 was increased in diabetes. Simvastatin increased the latency time. Simvastatin diminished the changes in oxidative stress markers and succeeded to ameliorate the diabetic induced cerebellar changes. Simvastatin enhanced Klotho and diminished Caspase-3 expression. Conclusion: Simvastatin can ameliorate diabetic induced cerebellar changes through minimizing oxidative stress, enhancement of Klotho expression and reduction of apoptosis.