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Hut, R. A.

Publications and source records attributed to Hut, R. A..

9 recordsLinked to original sources

Daylight exposure improves sleep and subsequent sleepiness

Study Objectives: The causal effects of daylight exposure on sleep remain poorly understood, particularly under real-world conditions. This study aimed to address this gap by examining the effects of an afternoon daylight intervention on subsequent sleep. Methods: Ten healthy participants (4 males; 19 to 28 years) completed two randomized 3-h afternoon outdoor walks under high-intensity light (HIL; clear goggles) or attenuated light (AL; neutral-density-filtered goggles; ~10 photopic lux) conditions. Light exposure was centered around the estimated crossover between the phase-advancing and phase-delaying portions of the light phase-response curve, individually determined from baseline dim light melatonin onset (DLMO). Subsequent nocturnal sleep was assessed using at-home polysomnography (PSG), and subjective sleepiness and sleep quality were assessed using the Karolinska Sleepiness Scale and Groningen Sleep Quality Scale, respectively. Differences between conditions and across time were examined using linear mixed-effects models. Results: There were no significant differences between conditions in DLMO timing or the phase angle between DLMO and sleep onset, indicating that the light manipulation did not produce a detectable shift in circadian phase. Sleep duration and self-reported sleep quality were also unchanged. However, nighttime delta power accumulated more rapidly following HIL exposure, accompanied by greater NREM sleep and reduced wakefulness after sleep onset (all p < 0.01). Participants were also significantly less sleepy upon awakening following HIL compared with AL exposure (p < 0.05). Conclusions: High-intensity natural daylight exposure may promote greater sleep intensity and reduce sleepiness upon awakening. These findings highlight a potential role for daytime light exposure in modulating subsequent sleep physiology and next-morning sleepiness, independent of changes in circadian phase.

neuroscience↗

Calorie Restriction-Induced Daily Hibernation in Mice Drives Cyclic DNA Damage and Repair

Hibernation consists of bouts of torpor, characterized by profound decreases in metabolism and body temperature (Tb), alternated with periods of euthermia called interbout arousals, during which normal metabolism and Tb resume. Seasonal hibernators accumulate DNA strand breaks during torpor, which are repaired during arousal. Here, we assess dynamics of DNA damage and repair during serial daily torpor in mice induced by 30% calorie restriction (CR) and investigate the effects of metabolic challenge on DNA repair. Serial daily torpor induced by CR in C57/BL6J mice of both sexes housed at 20{degrees}C lasts 6-12 hours. Like seasonal hibernators, DNA damage increases in CR-induced torpor and is repaired in the subsequent euthermic period, as evidenced by comet assay and {gamma}H2AX accumulation. To metabolically challenge animals, ambient temperature (Ta) was lowered to 4{degrees}C, since torpid mice defend a Tb of around 20{degrees}C or higher. Despite inducing a significant metabolic challenge, housing of torpid mice at 4{degrees}C does not increase DNA damage compared to 20{degrees}C housing. However, reducing Ta to 4{degrees}C during euthermia inhibits DNA repair. Interestingly, p21 levels increase in mice exposed to 4{degrees}C, indicating cell-cycle inhibition during exposure to 4{degrees}C. Thus, 30% CR induces daily cycles of torpor-induced DNA damage and euthermia-associated DNA repair in mice, and exposure to a Ta of 4{degrees}C during arousal inhibits DNA repair mounting a cell cycle inhibition response. Thus, the torpor-arousal cycle may be a contributing factor to the lifespan extension benefits of CR in mice, promoting genomic integrity and thereby cellular and tissue health.

physiology↗

In garden dormouse cerebral cortex, specific transcriptional programs exist for all major phases of hibernation

Hibernators cycle between torpor, a state of profound metabolic and thermoregulatory suppression, and brief arousals during which metabolic rate and body temperature rapidly return to euthermic levels. These repeated physiological pressures require robust mechanisms to preserve brain integrity. Because the cerebral cortex is not thought to control hibernation directly yet must remain viable throughout torpor and recover rapidly during arousal, it provides a useful model for studying neural adaptation to hibernation. We therefore performed RNA sequencing of cerebral cortex from garden dormice (Eliomys quercinus) sampled during summer euthermia (SE), early torpor (TE), late torpor (TL), early arousal (AE), and late arousal (AL). Differential expression analysis revealed strongly stage-specific transcriptional remodeling across the hibernation cycle. Entry into torpor (SE-TE) and the transition from early to late arousal (AE-AL) showed minimal change, with 16 and 2 differentially expressed genes (DEGs), respectively. In contrast, extensive regulation was observed during torpor progression (TE-TL; 576 DEGs) and especially during the transition from late torpor to early arousal (TL-AE; 697 DEGs). Intermediate numbers of DEGs were detected in AL-TE (260) and AL-SE (50). Principal component and enrichment analyses indicated that the dominant axes of variation were associated with RNA processing and proteostatic control, metabolic and redox-related adaptation, and changes in intracellular trafficking and protein handling. In addition, comparison of adjacent contrasts revealed a marked opposite-direction transcriptional reversal between TE-TL and TL-AE, consistent with coordinated reactivation of torpor-associated programs during arousal. Together, these findings support a model in which cortex adaptation to hibernation involves transcriptional reprogramming consistent with metabolic suppression during torpor progression, especially in pathways related to carbohydrate and central carbon metabolism, redox homeostasis, and cellular signalling, followed by rapid reversal of these programs during early arousal.

molecular biology↗

Beyond Lux: Methods for Species and Photoreceptor-Specific Quantification of Ambient Light for Mammals

BackgroundLight is a key environmental regulator of physiology and behaviour. Mistimed or insufficient light disrupts circadian rhythms and is associated with impaired health and well-being across mammals. Appropriate lighting is therefore crucial for indoor housed mammals. The most commonly used measurement for lighting is lux. However, this employs a spectral weighting function based on human perceived brightness and is not suitable for non-visual effects of light or use across species. In humans, a photoreceptor-specific (-opic) metrology system has been proposed as a more appropriate way of measuring light. ResultsHere we establish technology to allow this -opic measurement approach to be readily extended to any mammalian species, accounting for differences in photoreceptor types, photopigment spectral sensitivities, and eye anatomy. Since measuring photopigment spectral sensitivity can be hard to derive for novel animals and photoreceptors, we developed a high-throughput, easy-to-use, method to derive spectral sensitivities for recombinantly expressed melanopsins and use it to establish the spectral sensitivity of melanopsin from 12 non-human mammals. We further address the need for simple measurement strategies for species-specific -opic measures by developing an accessible online toolbox for calculating these units and validating an open hardware, low-cost, multichannel light sensor for point and click measurement. We finally demonstrate that species-specific -opic measurements are superior to photopic lux as predictors of physiological responses to light in mice and allow ecologically relevant comparisons of photosensitivity between species. ConclusionOur study demonstrates that measuring light more accurately using species-specific -opic units is superior to the existing unit of photopic lux and holds the promise of improvements to the health and welfare of animals, scientific research reproducibility, agricultural productivity, and energy usage.

neuroscience↗

Thermosensitivity of translation underlies the mammalian nocturnal-diurnal switch

Early mammals were nocturnal until the Cretaceous-Paleogene extinction enabled diurnal niche expansion. Diurnality evolved multiple times independently, but the mechanisms driving this shift remain unclear. We identify a conserved cell-intrinsic signal inversion that facilitates the transition from nocturnality to diurnality. Diurnal and nocturnal mammalian cells respond oppositely to temperature and osmotic cycles, mirroring species activity patterns. Cells exhibit differential global responses to temperature changes, including the phosphoproteome and protein synthesis. mTOR signaling is identified as a central mediator of this inversion, with diurnal mammals converging on modifications to mTOR and WNK pathways during evolution. Reducing mTOR activity induces nocturnal-to-diurnal shifting at cellular, tissue, and organismal levels. Therefore, the mTOR pathway is a cellular nexus that integrates energetic state and environmental signals to determine activity niche.

cell biology↗

Timing of increased temperature sensitivity coincides with nervous system development in winter moth embryos

Climate change is rapidly altering the environment and many species will need to genetically adapt their seasonal timing to keep up with these changes. Insect development rate is largely influenced by temperature, but we know little about the mechanisms underlying temperature sensitivity of development. Here we investigate seasonal timing of egg hatching in the winter moth, one of the few species which has been found to genetically adapt to climate change, likely through selection on temperature sensitivity of egg development rate. To study when during development winter moth embryos are most sensitive to changes in ambient temperature, we gave eggs an increase or decrease in temperature at different moments during their development. We measured their developmental progression and timing of egg hatching, and used fluorescence microscopy to construct a timeline of embryonic development for the winter moth. We found that egg development rate responded more strongly to temperature once embryos were in the fully extended germband stage. This is the phylotypic stage at which all insect embryos have developed a rudimentary nervous system. Furthermore, at this stage timing of ecdysone signaling determines developmental progression, which could act as an environment dependent gateway. Intriguingly, this may suggest that, from the phylotypic stage onward, insect embryos can start to integrate internal and environmental stimuli to actively regulate important developmental processes. As we found evidence that there is genetic variation for temperature sensitivity of egg development rate in our study population, such regulation could be a target of selection imposed by climate change.

evolutionary biology↗

Food and temperature change photoperiodic responses in two vole species: different roles for hypothalamic genes

Seasonal timing of reproduction in voles is driven by photoperiod. Here we hypothesize that a negative energy balance can modify spring-programmed photoperiodic responses in the hypothalamus, controlling reproductive organ development. We manipulated energy balance by the work-for-food protocol, in which voles were exposed to increasing levels of food scarcity at different ambient temperatures under long photoperiod. We reveal that common (Microtus arvalis) and tundra voles (Microtus oeconomus), reduce photoperiodic induced pars tuberalis thyroid-stimulating hormone {beta}-subunit (Tsh{beta}) expression to inhibit gonadal development when food is scarce. Reduction in gonadal size is more pronounced in tundra voles, in which the hypothalamic Kisspeptin (Kiss1) system seems involved in downregulating gonadal development, especially in males. Low temperature additionally leads to decreased hypothalamic RF-amide related peptide (Rfrp3) levels, which may facilitate further suppression of gonadal growth. Shutting off the photoperiodic-axis when food is scarce in spring may be an adaptive response to save energy, leading to delayed reproductive organ development until food resources are sufficient for reproduction, lactation and offspring survival. Defining the mechanisms through which metabolic cues modify photoperiodic responses will be important for a better understanding of how environmental cues impact reproduction. Summary statementThis study provides a better understanding of the molecular mechanism through which metabolic cues can modify photoperiodic responses, to adaptively adjust timing of reproductive organ development

neuroscience↗

Gonads or body? Differences in gonadal and somatic photoperiodic growth response in two vole species.

To optimally time reproduction, seasonal mammals use a photoperiodic neuroendocrine system (PNES) that measures photoperiod and subsequently drives reproduction. To adapt to late spring arrival at northern latitudes, a lower photoperiodic sensitivity and therefore a higher critical photoperiod for reproductive onset is necessary in northern species to arrest reproductive development until spring onset. Temperature-photoperiod relationships, and hence food availability-photoperiod relationships, are highly latitude dependent. Therefore, we predict PNES sensitivity characteristics to be latitude-dependent. Here, we investigated photoperiodic responses at different times during development in northern- (tundra/root vole, Microtus oeconomus) and southern vole species (common vole, Microtus arvalis) exposed to constant short (SP) or long photoperiod (LP). M. oeconomus grows faster under LP, whereas no photoperiodic effect on somatic growth is observed in M. arvalis. Contrastingly, gonadal growth is more sensitive to photoperiod in M. arvalis, suggesting that photoperiodic responses in somatic and gonadal growth can be plastic, and might be regulated through different mechanisms. In both species, thyroid-stimulating-hormone-{beta} subunit (Tsh{beta}) and iodothyronine-deiodinase 2 (Dio2) expression is highly increased under LP, whereas Tshr and Dio3 decreases under LP. High Tshr levels in voles raised under SP may lead to increased sensitivity to increasing photoperiods later in life. The higher photoperiodic induced Tshr response in M. oeconomus suggests that the northern vole species might be more sensitive to TSH when raised under SP. Species differences in developmental programming of the PNES, which is dependent on photoperiod early in development, may form part divergent breeding strategies evolving as part of latitudinal adaptation. Summary statementDevelopment of the neuroendocrine system driving photoperiodic responses in gonadal and somatic growth differ between the common and the tundra vole, indicating that they use a different breeding strategy.

neuroscience↗

Light effects on circadian and homeostatic regulation: alertness increases independent of time awake.

Light induced improvements in alertness are more prominent during night-time than during the day, indicating circadian regulation or wake duration related dependence. Relative contributions of both factors can be quantified using a forced desynchrony (FD) designs. Here we investigate alerting effects of light in a novel 4x18 hours FD protocol (5h sleep, 13h wake) under dim (6 mlux) and bright light (1159 mlux) conditions. Hourly saliva samples (melatonin and cortisol assessment) and 2-hourly test-sessions were used to assess effects of bright light on subjective and objective alertness (electroencephalography and performance). Results reveal (1) stable free-running cortisol rhythms with uniform phase progression under both light conditions, indicating that FD designs can be conducted under high intensity lighting, (2) subjective alerting effects of light depend on elapsed time awake, while (3) light consistently improves objective alertness independent of time awake. Three dimensional graphs reflecting light induced alertness improvements depending on wake duration related variation and circadian clock phase suggest that performance is improved during daytime, while subjective alertness remains unchanged. This suggests that light during office hours might be beneficial for performance, even though this may not be perceived as such.

neuroscience↗