Callosal Glia, GABAergic Interneurons, and Apoptotic Profiles in the Brains of Cypermethrin-Exposed Male and Female Rats

Background Cypermethrin, a Type II pyrethroid insecticide, has been linked to neurotoxicity. However, its effects on the corpus callosum, the brain's largest white matter tract essential for interhemispheric communication, remain poorly understood, particularly regarding sex-dependent vulnerability. This study examined sex-dependent effects of cypermethrin on the corpus callosum of Wistar rats, focusing on white matter integrity, glial populations, GABAergic interneurons, and apoptotic profiles. Methods Sixty adult Wistar rats (30 male, 30 female) were randomly allocated into six groups: male and female controls (corn oil), low-dose cypermethrin (6.25 mg/kg), and high-dose cypermethrin (12.5 mg/kg). Treatments were administered orally for 28 consecutive days. Behavioral assessment utilized the hole-board test. Biochemical analysis measured brain-derived neurotrophic factor (BDNF) and total protein. Immunohistochemical markers (GFAP, IBA-1, parvalbumin, cleaved caspase-3) and H&E staining were evaluated in the corpus callosum. Results Cypermethrin induced sex-dependent behavioral changes: males showed increased rearing frequency while females showed decreased rearing. BDNF concentrations significantly decreased in low-dose males (p = 0.0079) and females (p = 0.0039), with partial recovery in high-dose females. GFAP-positive astrocyte density decreased in exposed males but increased in low-dose females (p = 0.024). IBA-1-positive microglia decreased significantly in both sexes, particularly in low-dose groups (males: p = 0.0001; females: p = 0.0075). Parvalbumin-positive GABAergic interneuron density decreased in low-dose males (p = 0.029) and both female groups. Cleaved caspase-3 expression increased in all treated groups, with high-dose males most affected (p < 0.0001). H&E staining revealed dose-dependent cellular density reductions, greatest in high-dose males (p = 0.0001). Conclusion Cypermethrin induced sex-dependent white matter neurotoxicity, with males showing greater susceptibility than females.