Relative importance of intensity and spectrum of artificial light at night in disrupting behavior of a nocturnal rodent.

The influence of light spectral properties on circadian rhythms is of substantial interest to laboratory-based investigation of the circadian system and to field-based understanding of the effects of artificial light at night. The tradeoffs between intensity and spectrum regarding masking behaviors are largely unknown, even for well-studied organisms. We used a custom LED illumination system to document the response of wild type house mice (Mus musculus) to 1-hr nocturnal exposure of all combinations of four intensity levels (0.01, 0.5, 5, and 50 lx) and three correlated color temperatures (CCT; 1750, 1950, and 3000 K). Higher intensities of light (50 lx) suppressed cage activity substantially, and consistently more for the higher CCT light (91% for 3000 K; 53% for 1750 K). At the lower intensities (0.01 lx), mean activity was increased, with the greatest increases for the lowest CCT (12.3% increase at 1750 K; 3% increase at 3000 K). Multiple linear regression confirmed the influence of both CCT (p<0.001) and intensity (p<0.001) on changes in activity (r2=0.66, F9,171=3.33; p<0.001) with the scaled effect size of intensity 3.6 times greater than CCT. Activity suppression was significantly lower for male than female mice (p<0.0001). Assessment of light-evoked cFos expression in the suprachiasmatic nucleus at 50 lx showed no significant difference between high and low CCT exposure. The significant differences by spectral composition illustrate a need to account for light spectrum in circadian studies of behavior and confirm that spectral controls can mitigate some, but certainly not all, of the effects of light pollution on species in the wild.

Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington's disease.

Disturbances in sleep/wake cycles are common among patients with neurodegenerative diseases including Huntington's disease (HD) and represent an appealing target for chrono-nutrition-based interventions. In the present work, we sought to determine whether a low-carbohydrate, high-fat diet would ameliorate the symptoms and delay disease progression in the BACHD mouse model of HD. Adult WT and BACHD male mice were fed a normal or a ketogenic diet (KD) for 3 months. The KD evoked a robust rhythm in serum levels of ß-hydroxybutyrate and dramatic changes in the microbiome of male WT and BACHD mice. NanoString analysis revealed transcriptional changes driven by the KD in the striatum of both WT and BACHD mice. Disturbances in sleep/wake cycles have been reported in mouse models of HD and are common among HD patients. Having established that the KD had effects on both the WT and mutant mice, we examined its impact on sleep/wake cycles. KD increased daytime sleep and improved the timing of sleep onset, while other sleep parameters were not altered. In addition, KD improved activity rhythms, including rhythmic power, and reduced inappropriate daytime activity and onset variability. Importantly, KD improved motor performance on the rotarod and challenging beam tests. It is worth emphasizing that HD is a genetically caused disease with no known cure. Life-style changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of diet-based treatment strategies in a pre-clinical model of HD.