Chronic dim light at night provokes reversible depression-like phenotype: possible role for TNF

Abstract

The prevalence of major depression has increased in recent decades and women are twice as likely as men to develop the disorder. Recent environmental changes almost certainly have a role in this phenomenon, but a complete set of contributors remains unspecified. Exposure to artificial light at night (LAN) has surged in prevalence during the past 50 years, coinciding with rising rates of depression. Chronic exposure to LAN is linked to increased risk of breast cancer, obesity and mood disorders, although the relationship to mood is not well characterized. In this study, we investigated the effects of chronic exposure to 5 lux LAN on depression-like behaviors in female hamsters. Using this model, we also characterized hippocampal brain-derived neurotrophic factor expression and hippocampal dendritic morphology, and investigated the reversibility of these changes 1, 2 or 4 weeks following elimination of LAN. Furthermore, we explored the mechanism of action, focusing on hippocampal proinflammatory cytokines given their dual role in synaptic plasticity and the pathogenesis of depression. Using reverse transcription-quantitative PCR, we identified a reversible increase in hippocampal tumor necrosis factor (TNF), but not interleukin-1β, mRNA expression in hamsters exposed to LAN. Direct intracerebroventricular infusion of a dominant-negative inhibitor of soluble TNF, XPro1595, prevented the development of depression-like behavior under LAN, but had no effect on dendritic spine density in the hippocampus. These results indicate a partial role for TNF in the reversible depression-like phenotype observed under chronic dim LAN. Recent environmental changes, such as LAN exposure, may warrant more attention as possible contributors to rising rates of mood disorders.