Long-term exposure to constant light induces dementia, oxidative stress and promotes aggregation of sub-pathological Aβ42 in Wistar rats

Abstract

Constant exposure to light is prevalent in modern society where light noise, shift work, and jet lag is common. Constant light exposure disrupts circadian rhythm, induces stress and thus influences memory performance. We subjected adult male Wistar rats to a two-month exposure to constant light (LL), constant dark or normal light-dark cycles. Significant cognitive impairment and oxidative stress were observed in LL rats without a significant elevation in soluble Aβ1–42 levels. Next, we examined whether long-term exposure to constant light may accelerate dementia in a sub-pathological Aβ model of rats. Normal control rats received ACSF, AD rats received 440 pmol, and sub-pathological Aβ rats (Aβ(s)) received 220 pmol of human Aβ42 peptide in a single unilateral ICV administration. Sub-pathological Aβ rats exposed to constant light (LL + Aβ(s)) show significant memory deficits and oxidative damage, although not significantly different from LL rats. Additionally, constant light promoted aggregation of exogenous Aβ42 in LL + Aβ(s) rats shown by the presence of congophilic plaques. Furthermore, chronic fluoxetine treatment (5 mg/kg/day) rescued rats from the behavioral deficits, oxidative damage and amyloid aggregation. Whereas, rifampicin treatment (20 mg/kg/day) did not reverse the behavioral deficits or oxidative stress but rescued rats from amyloid plaque formation. It was concluded that constant light for two months induces behavioral deficits, oxidative stress, and accelerates aggregation of sub-pathological concentrations of human-Aβ42 peptides in Wistar rats, which is reversed by daily fluoxetine administration.