Age-Dependent Effects of Paraquat-Induced Parkinsonism on Serum Alpha-Synuclein Expression, Substantia Nigra Histoarchitecture and Neurobehaviour in Male Wistar Rats

ABSTRACT Background Paraquat (PQ), a widely used herbicide, has been implicated in Parkinson’s disease (PD)-like neurodegeneration through oxidative stress and alpha-synuclein (α-syn) dysregulation. Age is a critical determinant of vulnerability to neurotoxins. This study investigated age-dependent effects of paraquat-induced Parkinsonism on serum α-syn expression, substantia nigra histoarchitecture, and neurobehavior in male Wistar rats. Methods Sixty-three male Wistar rats were stratified into juvenile, young-adult, and adult cohorts and assigned to control, paraquat, or PQ+Recovery groups (n = 7). Paraquat (10 mg/kg, i.p.) was administered twice weekly for three weeks; recovery animals were monitored for two months. Neurobehavioral tests including hanging wire, open field, and Y-maze were conducted at baseline, post-exposure, and post-recovery. Serum and substantia nigra α-syn were quantified using ELISA, and histology assessed cytoarchitectural changes. Data were analyzed using t-tests and ANOVA (p ≤ 0.05). Results Neurobehavioral outcomes showed no significant differences in spontaneous alternation across cohorts. Latency-to-fall remained stable in young-adult and juvenile rats but declined in adult PQ+Recovery animals (p = 0.05). Line crossings decreased in adult paraquat rats (p = 0.02). Urine pools decreased significantly in young-adult paraquat (p = 0.0010) and PQ+Recovery groups (p = 0.0016), with group effects in young-adult (p = 0.007) and juvenile cohorts (p = 0.047). Substantia nigra α-syn showed no significant differences (p > 0.22); serum α-syn differed in young adults (p = 0.039), with reduced levels in the recovery group (p = 0.047). Histology revealed paraquat-induced neuronal degeneration was most severe in adults, and partial structural restoration after recovery. Conclusion Paraquat induces mild, age-dependent neurotoxic effects, with adults showing the greatest vulnerability. Differential serum α-syn responses and histological findings highlight developmental stage as a key modulator of susceptibility and recovery following environmental neurotoxin exposure.