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

Abstract

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.