Silent Neurotoxicity: Neurobehavioral Effects of Repeated Low-Dose Chlorpyrifos Exposure and Zinc-Mediated Protection

Abstract Chronic exposure to chlorpyrifos (CPF), a widely used organophosphorus insecticide, poses significant neurobehavioral risks, potentially mediated by oxidative stress and neuroinflammation. This study investigates the impact of repeated exposure to low dose of CPF exposure on neurobehavioral functions and hippocampal astrocyte activation and assesses the protective role of zinc supplementation. Adult male albino rats were assigned to control, CPF-treated, and CPF+zinc-treated groups. CPF was administered orally (18 mg/kg/day) for three weeks, with and without zinc sulfate (15 mg/kg/day). Neurobehavioral assessments included the Passive Avoidance and Open Field tests. Immunohistochemistry for Glial Fibrillary Acidic Protein (GFAP) was performed to evaluate astrocyte activation, with morphometric analysis quantifying GFAP immunoreactivity and the percentage of GFAP-positive astrocytes. The results show that CPF-treated rats exhibited significant memory and exploration deficits and increased anxiety-like behaviors compared to controls. These changes coincided with elevated GFAP immunoreactivity and an increased number of GFAP-positive astrocytes. Zinc co-administration ameliorated neurobehavioral impairments, reduced GFAP expression, and decreased astrocyte activation compared to CPF-only treatment. In conclusion, Repeated exposure to CPF was associated with neurobehavioral deficits and hippocampal astrocyte activation. Zinc supplementation showed a potential neuroprotective role, as evidenced by reduced astrocyte reactivity and partial improvement in behavioral performance.