Low-Intensity Constant Light During Early Postnatal Development Induces Sex-Specific Anxiety-Like Behaviour and Region- and Sex-Specific Changes in Circadian Gene Expression and RNA Editing

Abstract

Early-life exposure to light at night can disrupt the maturation of the circadian system and lead to long-lasting behavioural and molecular alterations. We exposed rat pups to constant light (LL; 16 lx) from birth (P0) to postnatal day 20, followed by a standard light-dark cycle (LD 12:12). At postnatal day 60, anxiety-like behaviour was assessed using the open field, elevated zero maze, and light/dark box. In parallel, we analysed circadian gene expression rhythms in the hippocampus, parietal cortex, frontal cortex, and olfactory bulbs, and examined A-to-I RNA editing and splicing in the hippocampus at P30. LL exposure increased body weight in males and tended to enhance anxiety-like behaviour, particularly in females. Locomotor activity during behavioural testing was reduced in both sexes, whereas circadian rhythms in constant darkness remained intact. At the molecular level, LL disrupted circadian gene expression in a brain region- and sex-specific manner. The hippocampus in males showed widespread loss of rhythmicity, while the parietal cortex was more affected in females. LL also reduced Adar2 expression rhythmicity and editing efficiency at functionally relevant sites in Gria2 and Htr2c, suggesting altered coupling between R/G editing and alternative splicing in Gria2. These findings demonstrate that low-intensity LL during a critical postnatal window can induce long-lasting, sex-specific alterations in behaviour and gene regulation. Our data provide the first mechanistic insight into how early environmental light exposure may shape long-term emotional and neurobiological outcomes.