Search Results (71)

Sleep disturbances are early hallmarks of Alzheimer’s disease (AD) and other dementias, yet the molecular mechanisms remain poorly understood. We previously showed that dipeptidyl aminopeptidase-like protein 6-knockout (DPP6-KO) mice exhibit accelerated neurodegeneration with synaptic loss, neuronal death, and circadian dysfunction resembling AD pathology. Here, we investigate whether DPP6 deficiency directly causes sleep dysregulation and assess age-dependent effects using wireless EEG/EMG telemetry, behavioral monitoring, and body temperature recordings. We found striking age-dependent sleep phenotypes in DPP6-KO mice. Adult (3-month) DPP6-KO mice showed hyperactivity-driven REM sleep increases, while aged (12-month) DPP6-KO mice developed insomnia with fragmented sleep architecture. Critically, aged DPP6-KO mice exhibited decreased REM latency, a biomarker of depression, which we confirmed by behavioral assays. Conversely, DPP6 overexpression in aged wild-type mice increased NREM duration and reduced sleep fragmentation, demonstrating a protective effect. Throughout aging, DPP6-KO mice showed dysregulated locomotor activity and body temperature rhythms, suggesting broader disruption of circadian and metabolic homeostasis. These findings establish DPP6 as a critical regulator of sleep architecture whose loss recapitulates key sleep disturbances observed in AD/dementia. The progressive nature of sleep dysfunction in DPP6-KO mice, from REM abnormalities to insomnia, parallels human disease progression and positions DPP6 as a potential therapeutic target for sleep-related symptoms in neurodegenerative disorders. Full article

Background/Objectives: Baichuan Baile (BCBL), a novel functional dietary formula, has been shown to exert antidepressant-like effects through modulation of the 5-HT system in our prior studies. Given the close neurobiological connections between depression and insomnia, along with its pharmacodynamic profile guided by TCM theory and nutritional assessments, BCBL is likely to possess beneficial effects against insomnia. However, this hypothesis and its underlying mechanisms require further validation. Methods: The chemical constituents of BCBL were analyzed by UPLC-Q-TOF-MS, and network pharmacology was applied to predict potential sleep-relevant targets and pathways. Subsequently, BCBL was evaluated for sedative-hypnotic effects using pentobarbital-induced hypnosis, locomotor activity, and polysomnography (EEG/EMG). Its therapeutic efficacy was further assessed in insomnia models induced by environmental stress, serotonin depletion, and rotarod-based sleep deprivation. The rotarod-induced chronic model was selected for mechanistic studies due to its sustained insomnia-like phenotype. Finally, key network-predicted targets were validated in this model through histopathology, Western blotting, and ELISA. Results: Pharmacological evaluation confirmed that BCBL significantly promoted sleep at both behavioral and EEG levels, confirming its sedative-hypnotic properties. BCBL mitigated environmental stress-triggered impairments in NREM sleep continuity and duration, and exerted protective effects against body weight loss and sleep disturbances in a serotonin depletion-induced insomnia model. In the rotarod sleep deprivation model, BCBL treatment increased spontaneous alternation rates and recognition indices, ameliorated hippocampal pathological alterations, and reduced hippocampal levels of HIF-1α, TNF-α, and IL-1β. Furthermore, BCBL elevated the p-GSK3β/GSK3β ratio and enhanced SIRT₁ expression in the hypothalamus. It also modulated the activity of key sleep–wake neurotransmitters/neuromodulators (serotonin, dopamine, adenosine, and glutamate) and key circadian rhythm regulators (BMAL₁, PER₂, and CLOCK) in this region. Conclusions: BCBL exhibits significant therapeutic efficacy against insomnia, indicating its potential as a dietary supplement for managing insomnia. Its mechanisms appear to involve anti-inflammatory effects, rebalancing of neurotransmitters/neuromodulators, and stabilization of circadian rhythm gene expression. Full article

Background/Objectives: The circadian regulator, circadian locomotor output cycles kaput (CLOCK), is well-established in maintaining sleep–wake rhythms, yet its cell-type-specific functions in sleep regulation remain largely unexplored. While ventromedial hypothalamic (VMH) prodynorphin (PDYN)-expressing (VMH^PDYN+) neurons are known to modulate homeostatic and motivational processes, their potential role in circadian sleep regulation has not been investigated. Methods: To address this, we developed mice with PDYN neuron-specific functional suppression of CLOCK activity (mClkΔ19) by interfering with their internal clock through Adeno-Associated Virus (AAV)-mediated overexpression of dominant-negative CLOCKΔ19 in PDYN-Cre mice. Results: We found that mClkΔ19 mice exhibited reduced locomotor activity during the dark phase, earlier activity peaks, and impaired rhythmicity of rapid eye movement (REM) and non-REM (NREM) sleep. Sleep analysis in mClkΔ19 mice showed selective reductions and fragmentation of light-phase REM sleep, more frequent sleep–wake transitions, and shorter REM cycles during the dark phase, indicating disrupted REM sleep timing. EEG spectral analysis in mClkΔ19 mice revealed decreased gamma activity during REM sleep in the light phase and an increase in delta activity coupled with decreased gamma during wakefulness in the dark phase. Conclusions: These findings suggest that the CLOCK activity in VMH^PDYN+ neurons is vital for circadian accuracy, REM sleep stability, and brain oscillations during sleep–wake cycles. Full article

Light is a fundamental ecological cue for insects, influencing physiological rhythms and behavior. We investigated how varying light intensities affect locomotion and foraging in H. axyridis color morphs, and examined the role of visual opsins. Three adult female morphs were assayed under white light at 1000, 5000, and 10,000 lx. Higher light intensity significantly elevated body temperature and locomotor activity across morphs, with the inherently dark f. conspicua morph exhibiting the greatest increases. Predation rates on pea aphids trended upward with intensity but differed significantly by morph: f. conspicua beetles consistently consumed more prey than f. succinea. RNAi knockdown of the UV-sensitive opsin HaUVSop-2 significantly reduced the crawling distance of satiated beetles under 5000 lux white light. Correspondingly, supplementation of white light with blue light (short wave) enhanced movement, whereas red supplementation increased aphid consumption. These results suggest that Short-wavelength light has the potential to stimulate the dispersal of ladybirds, whereas long-wavelength light may enhance predation on prey by increasing microenvironment temperature or improving prey recognition. We conclude that light intensity and spectrum jointly modulate H. axyridis behavior in a morph-dependent manner, mediated in part by visual opsins. Melanic morphs leverage thermal melanism to gain higher activity under bright light, implying an evolved trade-off between dispersal and stress tolerance. Our findings have practical implications: tailored lighting (e.g., blue-enhanced illumination to stimulate predation and dispersal of H. axyridis) could improve biological control efficacy in agroecosystems. Full article

Actigraphy quantifies human locomotor activity by measuring wrist acceleration via wearable devices at relatively high rates and converting it into lower-temporal-resolution activity values; however, the computational implementations of this data compression differ substantially across manufacturers. Building on our previous work comparing activity determination methods, we have investigated how they (e.g., digital filtering and data compression) influence nonparametric circadian rhythm analysis and sleep–wake scoring. In addition to our generalized actigraphic framework, we have also emulated the use of specific devices commonly employed in such sleep-related studies by applying their methods to raw actigraphic acceleration data we collected to demonstrate, through concrete real-life examples, how methodological choices may shape analytical outcomes. Additionally, we assessed whether nonparametric indicators could be derived directly from acceleration data without compressing them into activity values. Overall, our analysis revealed that all these analytical approaches to the sleep–wake cycle can be substantially affected by the manufacturer-dependent actigraphic methodology employed, with the observed effects traceable to distinct steps of the signal-processing pipeline, underscoring the necessity of cross-manufacturer harmonization from a clinically oriented perspective. Full article

Objective: This paper examines how rhythm-enhanced digital dance affects children’s motor abilities, cognitive performance, and neuromuscular synchronization. Methods: In a randomized repeated-measures study, 38 children (7–12 years) underwent three conditions: groove music-accompanied dance (GODA), conventional music dance (CODA), and non-musical physical activity (CON). Assessments of gross motor skills (using TGMD-3), executive function (using BRIEF and Stroop Test), and muscle coordination (using sEMG) were conducted. Results: Gross motor skills: GODA showed significantly higher TGMD scores in locomotor (p = 0.03) and ball skills (p = 0.02) compared to both CODA and CON (p < 0.001). Executive function: Inhibition and shifting dimensions showed significant post-intervention condition differences (p < 0.05). Muscle coordination: GODA exhibited greater β- and γ-band COH areas in the standing long jump compared to both CODA (p = 0.02) and CON (p < 0.001), and increased γ-band COH areas in single-leg balance compared to CODA (p = 0.02) and CON (p < 0.001). Conclusions: Combining rhythmic auditory stimulation with movement training offers a promising approach for integrated motor-cognitive development in children. Full article

Individuals with neurodevelopmental disorders (NDDs) often experience sleep disturbances and are frequently exposed to light during nighttime hours. Our previous studies using the Contactin-associated protein-like 2 (Cntnap2) knockout (KO) mouse model of NDDs demonstrated that nighttime light exposure adversely affected behavioral measures. In this study, we exposed wild-type (WT) and Cntnap2 KO mice to an ultradian lighting cycle (T7), which alternates 3.5 h of light and 3.5 h of darkness, hypothesizing that this lighting protocol would mimic the impact of nighttime light exposure seen in standard light–dark cycles with dim light at night (DLaN). However, adult WT and Cntnap2 KO mice held under the T7 cycle did not show the increased grooming behavior or reduced social interaction observed in Cntnap2 KO mice exposed to DLaN. The T7 cycle lengthened the circadian period and weakened the rhythm amplitude without abolishing rhythmicity in either genotype. Finally, opposite to DLaN, neither the T7 cycle nor constant darkness (DD) elicited an increase in cFos expression in the basolateral amygdala. These results demonstrate that the adverse effects of nighttime light exposure in an NDD model depend on the extent of the circadian disruption rather than light exposure alone, emphasizing the importance of circadian stability as a protective factor in NDDs. Full article

The circadian clock is a self-sustaining oscillator with a period of approximately 24 h, enabling organisms to anticipate daily recurring events, such as sunrise and sunset. Since the circadian period is not exactly 24 h and the environmental day length varies throughout the year, the clock must be periodically reset to align an organism’s physiology with the natural light/dark cycle. This synchronization, known as entrainment, is primarily regulated by nocturnal light, which can be replicated in laboratory settings using a 15 min light pulse (LP) and by assessing locomotor activity. An LP during the early part of the dark phase delays the onset of locomotor activity, resulting in a phase delay, whereas an LP in the late dark phase advances activity onset, causing a phase advance. The clock gene Period 2 (Per2) plays a key role in this process. To investigate its contributions, we examined the effects of Per2 deletion in neurons versus astrocytes using glia-specific GPer2 (Per2/GfapCre) knockout (KO) and neuronal-specific NPer2KO (Per2/NesCre) mice. All groups were subjected to Aschoff type II protocol, where an LP was applied at ZT14 or ZT22 and the animals were released into constant darkness. As control, no LP was applied. Phase shift, period, amplitude, total activity count, and rhythm instability were assessed. Our findings revealed that mice lacking Per2 in neurons (NPer2) exhibited smaller phase delays and larger phase advances compared to control animals. In contrast, mice with Per2 deletion specifically in glial cells including astrocytes (GPer2) displayed normal clock resetting. Interestingly, the absence of Per2 in either of the cell types resulted in a shorter circadian period compared to control animals. These results suggest that astrocytic Per2 is important for maintaining the circadian period but is not required for phase adaptation to light stimuli. Full article

Among physiological parameters, total locomotor activity (TLA) and heart rate (HR) are used as physiological indicators in animal welfare evaluations. The present study aimed to simultaneously record for 24 h the TLA and HR of ten clinically healthy horses housed in conventional individual boxes subjected to a natural photoperiod and temperature. An actigraphy-based data logger was placed on the headstall, and an equine HR monitor was placed around the chest to monitor TLA and HR, respectively. Activity was monitored with 5 min sampling intervals and HR with 5 s intervals. To make the data points uniform, the means of 5 min intervals were calculated. Both investigated parameters showed a daily rhythmicity with a diurnal acrophase (locomotor activity 17:05 ± 1:15 arbitrary unit; heart rate 16.40 ± 0.30 beats/min). Robustness of the rhythm was 17.95 ± 10.53% and 37.05 ± 0.63% for the TLA and HR. A positive correlation was observed between the two investigated parameters in each horse, r = 0.48 ± 0.07, p < 0.0001. Change in TLA is a good index for success of management. Its positive correlation with daily HR monitoring confirms the use of these two physiological parameters for an objective on-farm welfare assessment. The application of new technologies for the simultaneous recording of physiological indexes of animals’ welfare can be a useful instrument. Full article

Melatonin is an indolamine derived from tryptophan, which is highly conserved throughout evolution, including in zebrafish, where it controls important cellular processes, such as circadian rhythms, oxidative stress, inflammation, and mitochondrial homeostasis. These functions of melatonin and its synthesis route are quite similar to those in humans. One of the most important enzymes in melatonin synthesis is acetylserotonin O-methyltransferase (ASMT), the rate-limiting enzyme, which catalyzes its final step. Due to genome duplication, zebrafish has two genes for this enzyme, asmt1 and asmt2. These genes show differential expression; asmt1 is primarily expressed in the retina and the pineal gland, and asmt2 is expressed in peripheral tissues, indicating different functions. Therefore, the aim of this work was to develop a mutant model for each asmt gene and to analyze their phenotypic effects in zebrafish. The results showed that the loss of 80% of the asmt2 gene affected melatonin concentration and consequently disrupted the sleep/wake rhythm in larvae, decreasing by 50% the distance traveled. In contrast, the loss of asmt1 had a greater influence on the physical condition of adults, as locomotor activity decreased by 50%, and 75% showed malformations. These data reveal distinct functional roles of melatonin depending on their site of production that may affect the development of zebrafish. Full article

The diamondback moth, Plutella xylostella, is arguably the most economically impactful and widespread lepidopteran pest. Though the larval P. xylostella life stage is responsible for most of this cost through the consumption of crops, it is the adult form that spreads the pest to fresh crops all around the world, seeking them out in a seasonally expanding range. It is therefore important to understand the activity rhythms of adult P. xylostella in response to environmental cues such as light and temperature. We analysed diel rhythms in both adult clock gene expression and locomotor behaviour for the ROTH P. xylostella strain. Real-time quantitative PCR analyses of P. xylostella demonstrated diel rhythms for transcripts of the clock genes period and timeless under both entrained and free-running conditions indicating the presence of a functional daily timekeeping mechanism. However, adult locomotor rhythms exhibited temperature-driven and light-repressed regulation rather than circadian control. Thus, our analyses show a lack of coupling between the P. xylostella circadian clock and adult locomotor behaviour, which may be relevant in predicting the activity patterns of this agricultural pest. Full article

The suprachiasmatic nucleus (SCN) is the master regulator of the circadian system, modulating the daily timing of physiological and behavioral processes in mammals. While SCN synchronization is primarily driven by environmental light signals, sex hormones, particularly androgens, have a crucial role in regulating behavioral and reproductive processes to align with daily or seasonal cycles. SCN cell populations express receptors for sex steroid hormones, contributing to circadian synchronization mechanisms. Specifically, the activation of androgen receptors in the SCN has been shown to modulate clock gene expression and influence circadian rhythms. Rabbits, widely used in experimental research, exhibit unique behavioral patterns, including plasticity in circadian typology and seasonal variations in testosterone secretion. In this study, we explored, in male rabbits, the effect of castration on the daily pattern of locomotor activity and the expression of the clock protein PERIOD 1 (PER1) in the SCN. Our results show that castration significantly reduces daily locomotor activity and PER1 expression in the SCN. Moreover, a 4 h delay in the acrophase of PER1 expression was observed. We conclude that androgens have an important role in SCN synchronization mechanisms, contributing to the organization of physiological and behavioral events in this species. Full article

Circadian rhythms, the internal timekeeping systems governing physiological processes, significantly influence skin health, particularly in response to ultraviolet radiation (UVR). Disruptions in circadian rhythms can exacerbate UVR-induced skin damage and increase the risk of skin aging and cancer. This review explores how circadian rhythms affect various aspects of skin physiology and pathology, with a special focus on DNA repair. Circadian regulation ensures optimal DNA repair following UVR-induced damage, reducing mutation accumulation, and enhancing genomic stability. The circadian control over cell proliferation and apoptosis further contributes to skin regeneration and response to UVR. Oxidative stress management is another critical area where circadian rhythms exert influence. Key circadian genes like brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) modulate the activity of antioxidant enzymes and signaling pathways to protect cells from oxidative stress. Circadian rhythms also affect inflammatory and immune responses by modulating the inflammatory response and the activity of Langerhans cells and other immune cells in the skin. In summary, circadian rhythms form a complex defense network that manages UVR-induced damage through the precise regulation of DNA damage repair, cell proliferation, apoptosis, inflammatory response, oxidative stress, and hormonal signaling. Understanding these mechanisms provides insights into developing targeted skin protection and improving skin cancer prevention. Full article

Deprivation of sleep (DS) and its effects on circadian rhythm gene expression are not well understood despite their influence on various physiological and psychological processes. This study aimed to elucidate the changes in the expression of circadian rhythm genes following a night of sleep and DS. Their correlation with sleep architecture and physical activity was also examined. The study included 81 participants who underwent polysomnography (PSG) and DS with actigraphy. Blood samples were collected after PSG and DS. Expression levels of brain and muscle ARNT-like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), neuronal PAS domain protein 2 (NPAS2), period 1 (PER1), cryptochrome 1 (CRY1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) were analyzed using qRT-PCR. DS decreased the expression of CLOCK and BMAL1 while increasing PER1. PER1 expression correlated positively with total sleep time and non-rapid-eye-movement (NREM) sleep duration and negatively with sleep latency, alpha, beta and delta waves in the O1A2 lead. Physical activity during DS showed positive correlations with CLOCK, BMAL1, and CRY1. The findings highlight the role of PER1 in modulating sleep patterns, suggesting potential targets for managing sleep-related disorders. Further research is essential to deepen the understanding of these relationships and their implications. Full article

Sleep disturbances can disrupt the overall circadian rhythm. However, the impact of sleep deprivation on the circadian rhythm of the liver and its underlying mechanisms still requires further exploration. In this study, we subjected male mice to 5 days of sleep deprivation and performed liver transcriptome sequencing analysis at various time points within a 24-h period. Subsequently, we monitored the autonomic activity and food intake in these male mice for six days post-sleep deprivation. We observed alterations in sleep-wake and feeding rhythms in the first two days following sleep deprivation. Additionally, we also observed a decrease in 24-h serum-glucose levels. Liver transcriptome sequencing has shown that sleep deprivation induces the rhythmic transcription of a large number of genes, or alters the rhythmic properties of genes, which were then significantly enriched in the carbohydrate, lipid, and protein metabolism pathways. Our findings suggest that under conditions of prolonged sleep deprivation, the expression of metabolic-related genes in the liver was reset, leading to changes in the organism’s metabolic state to ensure energy supply to sustain prolonged wakefulness. Full article