Callosal glia, GABAergic interneurons, and apoptotic profiles in the brains of cypermethrin-exposed male and female rats

OBJECTIVE: Cypermethrin's effects on the corpus callosum, the brain's largest white matter tract essential for interhemispheric communication, remain unexplored, particularly regarding sex‑dependent vulnerability. We examined the effects of sub‑chronic cypermethrin exposure (6.25 and 12.5 mg/kg) on corpus callosum integrity in male and female Wistar rats, focusing on glial populations, GABAergic interneurons, and apoptosis, using biochemical (brain‑derived neurotrophic factor [BDNF] and total protein) and immunohistochemical markers (GFAP, IBA‑1, parvalbumin, cleaved caspase‑3). RESULTS: Cypermethrin caused 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). Collectively, cypermethrin induced sex‑dependent white matter neurotoxicity, with males showing greater susceptibility than females.