Age-related susceptibility to paraquat-induced neurotoxicity in male wistar rats: effects on neurobehaviour, substantia nigra cytoarchitecture, and alpha-synuclein levels

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder strongly associated with dopaminergic neuronal degeneration and alpha-synuclein pathology. Paraquat (PQ) has been implicated in Parkinsonian neurodegeneration; however, the influence of age on susceptibility to PQ-induced neuropathology remains insufficiently characterized. Aim This study investigated age-dependent effects of paraquat exposure on neurobehaviour, substantia nigra histomorphology, and serum alpha-synuclein levels in male Wistar rats. Methods Sixty-three male Wistar rats were assigned into juvenile, young adult, and adult age categories, each further subdivided into control, PQ-treated, and PQ+recovery groups. Paraquat (10 mg/kg, intraperitoneally) was administered twice weekly for three weeks. Recovery groups were maintained for a two-month post-exposure period. Neurobehavioral assessments were conducted to evaluate locomotor and anxiety-related functions. Serum and nigral alpha-synuclein concentrations were quantified using enzyme-linked immunosorbent assay (ELISA), while histological examination of the substantia nigra was performed to assess neuronal integrity. Results Adult rats exhibited a significant reduction in locomotor activity following PQ exposure ( p = 0.020) and showed more prominent histopathological alterations within the substantia nigra compared with juvenile and young-adult animals. Although improvement in tissue architecture was observed following paraquat withdrawal, residual alterations persisted, particularly in adults. Nigral alpha-synuclein concentrations did not differ significantly among treatment groups in any age cohort. Serum alpha-synuclein levels were similarly unchanged in most groups, except for a reduction observed in recovering young-adult animals ( p = 0.039). Conclusion Age influences vulnerability to PQ-induced neurotoxicity, with adult animals showing greater susceptibility to behavioral and histological damage. However, serum total alpha-synuclein levels did not consistently parallel central neuropathology, suggesting limited reliability as a standalone peripheral biomarker of PQ-induced Parkinsonism.