Search Results (31)

Hibernation in mammals entails profound physiological changes that are known to impact host-associated microbial communities, yet its effects on the gut microbiota of synanthropic bats remain underexplored. In this study, we investigated the gut bacterial composition and diversity of Nyctalus noctula before and during hibernation using high-throughput 16S rRNA amplicon sequencing. Fecal samples from individually banded bats were collected under controlled conditions at a rehabilitation center and analyzed for alpha and beta diversity, as well as differential taxonomic abundance. Hibernation was associated with a marked reduction in microbial diversity according to the Shannon and Simpson indices and a distinct restructuring of gut communities based on the Bray–Curtis dissimilarity index. Active bats exhibited a diverse microbiota enriched in facultative anaerobes, including Lactococcus, Enterococcus, and Escherichia–Shigella, while hibernating individuals were dominated by obligate anaerobes, such as Romboutsia and Paeniclostridium. These findings suggest a contraction and functional specialization of the gut microbiota during torpor, potentially reflecting adaptations to fasting, hypothermia, and reduced gut motility. Our results demonstrate that the bat’s gut microbiome is highly responsive to physiological status and underscore the importance of microbial ecology for understanding the host’s energy balance and health under seasonal contexts. Full article

Background: With renewed interest in long-duration space missions, there is growing exploration into synthetic torpor as a countermeasure to mitigate physiological stressors. Sedative agents, particularly those used in clinical anesthesia, have been proposed to replicate aspects of natural torpor, including reduced metabolic rate, core temperature, and brain activity. Objectives: This systematic review aims to evaluate the potential of sedative agents to induce torpor-like states suitable for extended spaceflight. The review specifically investigates their pharmacokinetics, pharmacodynamics, and performance under space-related stressors such as microgravity and ionizing radiation. Methods: We conducted a comprehensive search across multiple databases (e.g., PubMed, Scopus, Web of Science) for studies published from 1952 to 2024. Eligible studies included experimental, preclinical, and clinical investigations examining sedative agents (especially inhalation anesthetics) in the context of metabolic suppression or space-relevant conditions. Screening, selection, and data extraction followed PRISMA guidelines. Results: Out of the screened records, 141 studies met the inclusion criteria. These were thematically grouped into seven categories, including torpor physiology, anesthetic uptake, metabolism, and inhalation anesthetics. Sedative agents showed variable success in inducing torpor-like states, with inhalation anesthetics demonstrating promising metabolic effects. However, concerns remain regarding delivery methods, safety, rewarming, and the unknown effects of prolonged use in space environments. Conclusions: Sedative agents, particularly volatile anesthetics, hold potential as tools for inducing synthetic torpor in space. Nevertheless, significant knowledge gaps and technical challenges persist. Further targeted research is required to optimize these agents for safe, controlled use in spaceflight settings. Full article

Little brown bats (Myotis lucifugus) cluster in hibernacula sites over winter, in which they use metabolic rate depression (MRD) to facilitate entrance and exit of hibernation. This study used small RNA sequencing and bioinformatic analyses to identify differentially regulated microRNAs (miRNAs) and to predict their downstream effects on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms in the skeletal muscle of torpid M. lucifugus as compared to euthermic controls. We observed a subset of ten miRNAs whose expression changed during hibernation, with predicted functional roles linked to cell cycle processes, downregulation of protein degradation via ubiquitin-mediated proteolysis, downregulation of signaling pathways, including MAPK, p53, mTOR, and TGFβ, and downregulation of cytoskeletal and vesicle trafficking terms. Taken together, our results indicate miRNA regulation corresponding to both widely utilized MRD survival strategies, as well as more hibernation- and tissue-specific roles in M. lucifugus, including skeletal muscle atrophy resistance via myostatin inhibition and insulin signaling suppression. Full article

Hibernating mammals experience severe hemodynamic changes over the torpor–arousal cycle, with oxygen consumption reaching peaks during the early stage of torpor to re-enter arousal. Melatonin (MT) can improve mitochondrial function and reduce oxidative stress and inflammation. However, the regulatory mechanisms of MT action on the vascular protective function of hibernators are still unclear. Morphology, hemodynamic, mitochondrial oxidative stress, and inflammatory factors of the carotid artery were assessed in ground squirrels who were sampled during summer active (SA), late torpor (LT), and interbout arousal (IBA) conditions. Changes were assessed by methods including hematoxylin and eosin staining, color Doppler ultrasound, ELISA, Western blots, and qPCR. Changes in arterial blood and serum melatonin were also measured by blood gas analyzer and ELISA, whereas mitochondrial oxidative stress and inflammation factors of primary vascular smooth muscle cells (VSMCs) were assessed by qPCR. (1) Intima-media carotid thickness, peak systolic velocity (PSV), end diastolic blood flow velocity (EDV), maximal blood flow rate (Vmax) and pulsatility index (PI) were significantly decreased in the LT group as compared with the SA group, whereas there were no difference between the SA and IBA groups. (2) PO₂, oxygen saturation, hematocrit and PCO₂ in the arterial blood were significantly increased, and pH was significantly decreased in the LT group as compared with the SA and IBA groups. (3) The serum melatonin concentration was significantly increased in the LT group as compared with the SA and IBA groups. (4) MT treatment significantly reduced the elevated levels of LONP1, NF-κB, NLRP3 and IL-6 mRNA expression of VSMCs under hypoxic conditions. (5) Protein expression of HSP60 and LONP1 in the carotid artery were significantly reduced in the LT and IBA groups as compared with the SA group. (6) The proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the carotid artery of the LT group as compared with the SA and IBA groups. The carotid artery experiences no oxidative stress or inflammatory response during the torpor–arousal cycle. In addition, melatonin accumulates during torpor and alleviates oxidative stress and inflammatory responses caused by hypoxia in vitro in VSMCs from ground squirrels. Full article

The green shore crab (Carcinus maenas) is native to Western Europe but has spread around the globe and is described as one of the top 100 worst invasive species. On the east coast of North America, their northern-most limit is the island of Newfoundland, Canada, where they can experience water temperatures as low as −1 °C. We investigated the physiological responses of C. maenas to a temperature reduction regime as well as to long-term acclimation to temperatures representative of winter (2 °C) and summer (12 °C) in Newfoundland. Heart rate, oxygen consumption and estimated energy expenditure declined steadily with decreasing temperature, but a marked change was observed between 6 and 4 °C, with lowest levels recorded in 2 °C. After long-term acclimation to 2 °C there was a sustained reduction in physiological parameters. Even though these physiological parameters were very low in 2 °C, the crabs still exhibited intermittent activity. This supports the presence of a dormancy, rather than true torpor/hibernation below 5 °C, in which crabs will continue to actively move and feed, albeit much more slowly. The population in Newfoundland contains haplotypes from both the invasive northern and southern lineages, and they appear to retain a similar low temperature response compared with most other populations of green crab from both their native and expanded range. Full article

Pseudogymnoascus destructans is a psychrophilic fungus that causes white-nose syndrome (WNS), an emerging disease in North America. This fungus has caused unprecedented population declines. It has also been described in Europe and Asia, where it has not caused significant mortality. The first evidence of WNS in North America came from a photograph of a hibernating bat taken during the winter of 2005–2006 in a cave near Albany, New York. P. destructans develops when the body temperature decreases during winter hibernation. This fungus thrives in humid and cold conditions characteristic of caves. Infected bats can develop visible white fungal growth on the nose, ears, and wings, and awaken more frequently from torpor. It leads to physiologic changes that result in weight loss, dehydration, electrolyte imbalances, and the death of bats. The fungi can persist in the environments of underground bat hibernation sites and are believed to spread primarily by the natural movements of infected bats. Also, there is a strong possibility that it may also be transmitted by humans inadvertently carrying the fungus from cave to cave on their clothing and gear. WNS has a big impact on bat populations with high levels of mortality, particularly endangered species. Some populations will take many years to recover. The decline of bats also has an impact on the spread of diseases, since many species of bat feed on insect carriers of several pathogens. Full article

Alzheimer’s disease (AD) is the most common cause of dementia worldwide and yet remains without effective therapy. Amongst the many proposed causes of AD, the mitochondrial cascade hypothesis is gaining attention. Accumulating evidence shows that mitochondrial dysfunction is a driving force behind synaptic dysfunction and cognitive decline in AD patients. However, therapies targeting the mitochondria in AD have proven unsuccessful so far, and out-of-the-box options, such as hibernation-derived mitochondrial mechanisms, may provide valuable new insights. Hibernators uniquely and rapidly alternate between suppression and re-activation of the mitochondria while maintaining a sufficient energy supply and without acquiring ROS damage. Here, we briefly give an overview of mitochondrial dysfunction in AD, how it affects synaptic function, and why mitochondrial targeting in AD has remained unsuccessful so far. We then discuss mitochondria in hibernation and daily torpor in mice, covering current advancements in hibernation-derived mitochondrial targeting strategies. We conclude with new ideas on how hibernation-derived dual mitochondrial targeting of both the ATP and ROS pathways may boost mitochondrial health and induce local synaptic protein translation to increase synaptic function and plasticity. Further exploration of these mechanisms may provide more effective treatment options for AD in the future. Full article

Mammalian hibernation is composed of multiple episodes of torpor bout, separated by phases of interbout arousal. During torpor, the skeletal muscles of mammals are undoubtedly inactive, but it has been proven to mitigate disuse atrophy. While interbout arousal has been implicated in the prevention of muscle atrophy, the underlying mechanisms sustaining muscle contraction remain to be explored. In the present study, Daurian ground squirrels (Spermophilus dauricus) were divided into four groups: pre-hibernation (PRE), torpor (TOR), interbout arousal (IBA), and post-hibernation (POST). The contractile performance of slow-twitch soleus muscle (SOL) and fast-twitch extensor digitorum longus muscle (EDL) was detected both in situ and in vitro. Concurrently, mitochondrial respiratory chain complex activity in these muscles was quantified. Our findings revealed that in situ contractile properties of both muscles, including force, power output, time duration, and force development/relaxation rates of twitch contraction, and force and power output of tetanic contraction declined in the TOR group compared to the PRE group, but improved in the IBA and POST groups. Fatigue resistance of muscles, determined by the power output of repetitive tetanic contractions in situ, decreased in the TOR group but recovered in the IBA and POST groups. In vitro studies demonstrated that tetanic contraction power output in isolated muscles increased with muscle temperature in both TOR and IBA groups. However, at the same temperature, power output was consistently lower in the TOR group compared to the IBA group. Moreover, the activity of the mitochondrial respiratory chain complex, especially Complexes I and II, decreased in the TOR group but showed recovery in the IBA and POST groups. These findings suggest that both the contractile performance and fatigue resistance of mammalian skeletal muscle are compromised during torpor but can be improved during interbout arousal and post-hibernation. The rebound in body temperature and rise in mitochondrial respiratory chain complex activity in skeletal muscle are involved in enhancing contractile performance and fatigue resistance. This study suggests that interbout arousal functions as a vital temporal interval during which skeletal muscles can transition from the inactivity induced by torpor to a state of restored contractile functionality. Thus, interbout arousal serves as a behavioral safeguard against disuse-induced damage to skeletal muscles during hibernation. Full article

Hypothermia is a promising clinical therapy for acute injuries, including neural damage, but it also faces practical limitations due to the complexities of the equipment and procedures required. This study investigates the use of the A1 adenosine receptor (A1AR) agonist N6-cyclohexyladenosine (CHA) as a more accessible method to induce steady, torpor-like hypothermic states. Additionally, this study investigates the protective potential of CHA against LPS-induced sepsis and neuroinflammation. Our results reveal that CHA can successfully induce a hypothermic state by activating a neuronal circuit similar to the one that induces physiological torpor. This state is characterized by maintaining a steady core body temperature below 28 °C. We further found that this torpor-like state effectively mitigates neuroinflammation and preserves the integrity of the blood–brain barrier during sepsis, thereby limiting the infiltration of inflammatory factors into the central nervous system. Instead of being a direct effect of CHA, this protective effect is attributed to inhibiting pro-inflammatory responses in macrophages and reducing oxidative stress damage in endothelial cells under systemic hypothermia. These results suggest that A1AR agonists such as CHA could potentially be potent neuroprotective agents against neuroinflammation. They also shed light on possible future directions for the application of hypothermia-based therapies in the treatment of sepsis and other neuroinflammatory conditions. Full article

Pelodiscus sinensis (P. sinensis) is a commonly cultivated turtle species with a habit of hibernation. To study the changes in histone expression and methylation of P. sinensis during hibernation induction, a model was established by artificial induction. Physiological and metabolic indices were measured, and the expression and localization of histone (H1, H2A, H2B, H3, and H4) and methylation-related genes (ASH2L, KMT2A, KMT2E, KDM1A, KDM1B, and KDM5A) were measured by quantitative PCR, immunohistochemistry, and Western blot analysis. The results indicated that the metabolism, antioxidation index, and relative expression of histone methyltransferase were significantly decreased (p < 0.05), whereas the activity and expression of histone demethyltransferase were significantly increased (p < 0.05). Although our results showed significant changes in physiological and gene expression after hibernation induction, we could not confirm that P. sinensis entered deep hibernation. Therefore, for the state after cooling-induced hibernation, cold torpor might be a more accurate description. The results indicate that the P. sinensis can enter cold torpor through artificial induction, and the expression of histones may promote gene transcription. Unlike histones expressed under normal conditions, histone methylation may activate gene transcription during hibernation induction. Western blot analysis revealed that the ASH2L and KDM5A proteins were differentially expressed in the testis at different months (p < 0.05), which may perform a role in regulating gene transcription. The immunohistochemical localization of ASH2L and KDM5A in spermatogonia and spermatozoa suggests that ASH2L and KDM5A may perform a role in mitosis and meiosis. In conclusion, this study is the first to report changes in histone-related genes in reptiles, which provides insight for further studies on the physiological metabolism and histone methylation regulation of P. sinensis during the hibernation induction and hibernation period. Full article

Bats spend most of their lives resting, socializing, and raising their young in roosts. Roost conditions may affect the lifetime energy expenditure of bats, and this could, in turn, influence fitness of individuals. Different kinds of roosts impose different microclimatic conditions that can affect the thermal balances of bats that use them. Bats thermoregulate by using both physiological mechanisms (such as changes in conductance) and behavioral responses (huddling or active search of certain microclimates). We hypothesized that the contribution of these thermoregulatory strategies would differ depending on the roost type that bats use. To test this idea, we collated data from the literature on metabolic rate (MR), body temperature (T_b), ambient temperature at which MR and T_b were collected, roost type, and diet for 43 species of bats spanning eleven families. From these data, we calculated, for each species, the wet conductance and the area of the thermoregulatory polygon (TRP) as a proxy for the physiological thermoregulatory capabilities of bats. We found that, after controlling for phylogeny, wet conductance and the area of the TRP were higher in bats that use more exposed roosts than in those bats who use roosts that can buffer environmental conditions. Our results suggest that energy expenditure is similar for all species, but in bats that live in more exposed roosts, the contribution of physiological responses was more important than behavior at the entire range of environmental temperatures, whereas bats in more protected roosts seem to rely more on behavioral responses to thermoregulate. Considering that roosts represent valuable resources, the availability of roosts with the proper microclimatic conditions could determine the patterns of distribution of bat populations. Full article

The utilisation of synthetic torpor for interplanetary travel once seemed farfetched. However, mounting evidence points to torpor-induced protective benefits from the main hazards of space travel, namely, exposure to radiation and microgravity. To determine the radio-protective effects of an induced torpor-like state we exploited the ectothermic nature of the Danio rerio (zebrafish) in reducing their body temperatures to replicate the hypothermic states seen during natural torpor. We also administered melatonin as a sedative to reduce physical activity. Zebrafish were then exposed to low-dose radiation (0.3 Gy) to simulate radiation exposure on long-term space missions. Transcriptomic analysis found that radiation exposure led to an upregulation of inflammatory and immune signatures and a differentiation and regeneration phenotype driven by STAT3 and MYOD1 transcription factors. In addition, DNA repair processes were downregulated in the muscle two days’ post-irradiation. The effects of hypothermia led to an increase in mitochondrial translation including genes involved in oxidative phosphorylation and a downregulation of extracellular matrix and developmental genes. Upon radiation exposure, increases in endoplasmic reticulum stress genes were observed in a torpor+radiation group with downregulation of immune-related and ECM genes. Exposing hypothermic zebrafish to radiation also resulted in a downregulation of ECM and developmental genes however, immune/inflammatory related pathways were downregulated in contrast to that observed in the radiation only group. A cross-species comparison was performed with the muscle of hibernating Ursus arctos horribilis (brown bear) to define shared mechanisms of cold tolerance. Shared responses show an upregulation of protein translation and metabolism of amino acids, as well as a hypoxia response with the shared downregulation of glycolysis, ECM, and developmental genes. Full article

Hypometabolism and hypothermia are common reactions of birds and mammals to cope with harsh winter conditions. In small mammals, the occurrence of hibernation and daily torpor is entrained by photoperiod, and the magnitude of hypometabolism and decrease of body temperature (T_b) is influenced by the dietary supply of essential polyunsaturated fatty acids. We investigated whether similar effects exist in a non-hibernating large mammal, the red deer (Cervus elaphus). We fed adult females with pellets enriched with either linoleic acid (LA) or α-linolenic acid (ALA) during alternating periods of ad libitum and restricted feeding in a cross-over experimental design. Further, we scrutinized the role of photoperiod for physiological and behavioral seasonal changes by manipulating the amount of circulating melatonin. The deer were equipped with data loggers recording heart rate, core and peripheral T_b, and locomotor activity. Further, we regularly weighed the animals and measured their daily intake of food pellets. All physiological and behavioral parameters measured varied seasonally, with amplitudes exacerbated by restricted feeding, but with only few and inconsistent effects of supplementation with LA or ALA. Administering melatonin around the summer solstice caused a change into the winter phenotype weeks ahead of time in all traits measured. We conclude that red deer reduce energy expenditure for thermoregulation upon short daylength, a reaction amplified by food restriction. Full article

Temperature changes and periods of detrimental cold occur frequently for many organisms in their natural habitats. Homeothermic animals have evolved metabolic adaptation strategies to increase mitochondrial-based energy expenditure and heat production, largely relying on fat as a fuel source. Alternatively, certain species are able to repress their metabolism during cold periods and enter a state of decreased physiological activity known as torpor. By contrast, poikilotherms, which are unable to maintain their internal temperature, predominantly increase membrane fluidity to diminish cold-related damage from low-temperature stress. However, alterations of molecular pathways and the regulation of lipid-metabolic reprogramming during cold exposure are poorly understood. Here, we review organismal responses that adjust fat metabolism during detrimental cold stress. Cold-related changes in membranes are detected by membrane-bound sensors, which signal to downstream transcriptional effectors, including nuclear hormone receptors of the PPAR (peroxisome proliferator-activated receptor) subfamily. PPARs control lipid metabolic processes, such as fatty acid desaturation, lipid catabolism and mitochondrial-based thermogenesis. Elucidating the underlying molecular mechanisms of cold adaptation may improve beneficial therapeutic cold treatments and could have important implications for medical applications of hypothermia in humans. This includes treatment strategies for hemorrhagic shock, stroke, obesity and cancer. Full article

The small, ubiquitin-like modifier (SUMO) is a post-translational modifier with a profound influence on several key biological processes, including the mammalian stress response. Of particular interest are its neuroprotective effects, first recognized in the 13-lined ground squirrel (Ictidomys tridecemlineatus), in the context of hibernation torpor. Although the full scope of the SUMO pathway is yet to be elucidated, observations of its importance in managing neuronal responses to ischemia, maintaining ion gradients, and the preconditioning of neural stem cells make it a promising therapeutic target for acute cerebral ischemia. Recent advances in high-throughput screening have enabled the identification of small molecules that can upregulate SUMOylation, some of which have been validated in pertinent preclinical models of cerebral ischemia. Accordingly, the present review aims to summarize current knowledge and highlight the translational potential of the SUMOylation pathway in brain ischemia. Full article