Effect of prolonged exposure to different lighting conditions on MPTP-induced motor dysfunction and cognitive performance in male rats

Circadian rhythm disruption has been increasingly implicated in neurodegenerative diseases, including Parkinson's disease (PD). While motor impairments in PD are well-established, the impact of chronic circadian misalignment on both motor and cognitive dysfunctions remains underexplored. This study investigates the effect of prolonged exposure to different lighting conditions on MPTP-induced motor and cognitive deficits in a rat model. A total of 100 adult male Wistar rats were divided into five groups with different light-dark cycle conditions: standard 12-h light/12-h dark (12 L:12D), constant light (24 L), constant darkness (24D), 20-h light/4-h dark (20 L:4D), and 4-h light/20-h dark (20D:4 L). After 60 d of exposure to these conditions, each group was further divided into Parkinsonian (MPTP-treated) and non-Parkinsonian (saline-treated) subgroups. MPTP hydrochloride (25 µg/kg) was administered intranasally to induce Parkinsonism. Behavioral assessments, including the beam balance test, open field test, Y-maze test, and shuttle box test, were conducted to evaluate motor coordination and cognitive function. Immunohistochemical analyses of α-synuclein (α-syn) accumulation in the substantia nigra (SNc) and tyrosine hydroxylase (TH) expression in the suprachiasmatic nucleus (SCN) were performed. Data were analyzed using t test, one-way ANOVA and Tukey's post hoc test. MPTP administration significantly impaired motor function, as evidenced by increased crossing time in the beam balance test (p < 0.001) and reduced locomotor activity in the open field test (p < 0.01). Prolonged exposure to different lighting conditions further exacerbated these deficits, particularly in the 24 L and 20 L:4D groups (p < 0.0001). Cognitive assessments revealed that MPTP-treated rats exhibited marked deficits in working memory (Y-maze, p < 0.05) and associative learning (shuttle box, p < 0.01), with the most severe impairments observed in groups subjected to extreme light-dark alterations. Immunohistochemical analyses demonstrated significantly increased α-syn accumulation in the SNc (p < 0.0001) and decreased TH expression in the SCN (p < 0.001), particularly in MPTP-treated rats under photoperiod disruption. Chronic photoperiod disruption exacerbates MPTP-induced motor dysfunction, cognitive impairment, and neurodegeneration. Targeting circadian regulation may offer a potential therapeutic approach for mitigating neurodegenerative progression in PD.