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1.
J Clin Invest ; 134(18)2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39286982

RESUMO

Maintaining protein homeostasis (proteostasis) requires precise control of protein folding and degradation. Failure to properly respond to stresses disrupts proteostasis, which is a hallmark of many diseases, including cataracts. Hibernators are natural cold-stress adaptors; however, little is known about how they keep a balanced proteome under conditions of drastic temperature shift. Intriguingly, we identified a reversible lens opacity phenotype in ground squirrels (GSs) associated with their hibernation-rewarming process. To understand this "cataract-reversing" phenomenon, we first established induced lens epithelial cells differentiated from GS-derived induced pluripotent stem cells, which helped us explore the molecular mechanism preventing the accumulation of protein aggregates in GS lenses. We discovered that the ubiquitin-proteasome system (UPS) played a vital role in minimizing the aggregation of the lens protein αA-crystallin (CRYAA) during rewarming. Such function was, for the first time to our knowledge, associated with an E3 ubiquitin ligase, RNF114, which appears to be one of the key mechanisms mediating the turnover and homeostasis of lens proteins. Leveraging this knowledge gained from hibernators, we engineered a deliverable RNF114 complex and successfully reduced lens opacity in rats with cold-induced cataracts and zebrafish with oxidative stress-related cataracts. These data provide new insights into the critical role of the UPS in maintaining proteostasis in cold and possibly other forms of stresses. The newly identified E3 ubiquitin ligase RNF114, related to CRYAA, offers a promising avenue for treating cataracts with protein aggregates.


Assuntos
Catarata , Hibernação , Cristalino , Sciuridae , Ubiquitina-Proteína Ligases , Animais , Catarata/genética , Catarata/patologia , Catarata/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Cristalino/metabolismo , Cristalino/patologia , Temperatura Baixa , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteostase , Células-Tronco Pluripotentes Induzidas/metabolismo , Cristalinas/metabolismo , Cristalinas/genética , Ratos
2.
Biol Lett ; 20(9): 20240291, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39288816

RESUMO

Hibernators face an energetic dilemma in the autumn at northern latitudes; while temperatures and food availability decrease, hibernating species need to build fat deposits to survive the winter. During this critical fattening phase, insectivorous boreal bats use torpor to build and conserve their reserves. However, we still know little about temporal variability in torpor use employed by bats during the prehibernation fattening period and how decreasing temperatures and food availability in combination with increasing individual body mass impact this. Here, we present two general hypotheses for explaining temporal torpor patterns observed in a boreal bat (Eptesicus nilssonii), in which torpor use (i) facilitates rapid mass gain or (ii) conserves stored body mass. Although temporally separated in our dataset, data on temperature, insect abundance and body mass throughout the prehibernation period indicate that E. nilssonii reaches the majority of its overwintering mass before the onset of increasing daytime and night-time torpor use. In combination with low food availability by this point in time, these observations suggest torpor expression may be intended to conserve gained reserves rather than facilitate mass gain. Our study is intended as a first proof of concept for disentangling temporal drivers of torpor in bats during the prehibernation fattening phase.


Assuntos
Quirópteros , Hibernação , Torpor , Animais , Quirópteros/fisiologia , Torpor/fisiologia , Hibernação/fisiologia , Estações do Ano , Peso Corporal
3.
Sci Rep ; 14(1): 20562, 2024 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232030

RESUMO

The search for biomarkers for the early diagnosis of neurodegenerative diseases is a growing area. Numerous investigations are exploring minimally invasive and cost-effective biomarkers, with the detection of phosphorylated Tau (pTau) protein emerging as one of the most promising fields. pTau is the main component of the paired helical filaments found in the brains of Alzheimer's disease cases and serves as a precursor in the formation of neurofibrillary tangles (NFTs). Recent research has revealed that analysis of p-Tau181, p-Tau217 and p-Tau231 in blood may be an option for detecting the preclinical stage of Alzheimer's disease. In this study, we have analyzed the values of pTau 181 in the serum of Syrian hamsters during hibernation. Naturally, over the course of hibernation, these animals exhibit a reversible accumulation of pTau in the brain tissue, which rapidly disappears upon awakening. A biosensing system based on the interferometric optical detection method was used to measure the concentration of pTau181 protein in serum samples from Syrian hamsters. This method eliminates the matrix effect and amplifies the signal obtained by using silicon dioxide nanoparticles (SiO2 NPs) biofunctionalized with the αpTau181 antibody. Our results indicate a substantial increase in the serum concentration of pTau in threonine-181 during hibernation, which disappears completely 2-3 h after awakening. Investigating the mechanism by which pTau protein appears in the blood non-pathologically may enhance current diagnostic techniques. Furthermore, since this process is reversible, and no tangles are detected in the brains of hibernating hamsters, additional analysis may contribute to the discovery of improved biomarkers. Additionally, exploring drugs targeting pTau to prevent the formation of tangles or studying the outcomes of any pTau-targeted treatment could be valuable.


Assuntos
Hibernação , Mesocricetus , Proteínas tau , Animais , Proteínas tau/metabolismo , Proteínas tau/sangue , Fosforilação , Cricetinae , Biomarcadores/sangue , Nível de Alerta/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/sangue , Masculino , Encéfalo/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-39097140

RESUMO

Muscle and bone are cooperatively preserved in Daurian ground squirrels (Spermophilus dauricus) during hibernation. As such, we hypothesized that IGF-1 and myostatin may contribute to musculoskeletal maintenance during this period. Thus, we systematically assessed changes in the protein expression levels of IGF-1 and myostatin, as well as their corresponding downstream targets, in the vastus medialis (VM) muscle and femur in Daurian ground squirrels during different stages. Group differences were determined using one-way analysis of variance (ANOVA). Results indicated that the co-localization levels of IGF-1 and its receptor (IGF-1R) increased by 50% during the pre-hibernation period (PRE) and by 35% during re-entry into torpor (RET) compared to the summer active period (SA). The phosphorylation level of FOXO1 in the VM muscle increased by 50% in the torpor (TOR) group and by 82% in the inter-bout arousal (IBA) group compared to the PRE group. The phosphorylation level of SGK-1 increased by 54% in the IBA group and by 62% in the RET group compared to the SA group. In contrast, the protein expression of IGF-1 and phosphorylation levels of PI3K, Akt, mTOR, and GSK3ß in the VM muscle showed no obvious differences among the different groups. ß-catenin protein expression was up-regulated by 84% in the RET group compared to the SA group, while the content of IGF-1 protein, correlation coefficients of IGF-1 and IGF-1R, and phosphorylation levels of PI3K, Akt, and GSK3ß in the femur showed no significant differences among groups. Regarding myostatin and its downstream targets, myostatin protein expression decreased by 70% in the RET group compared to the SA group, whereas ActRIIB protein expression and Smad2/3 phosphorylation in the VM muscle showed no obvious differences among groups. Furthermore, Smad2/3 phosphorylation decreased by 58% in the TOR group and 53% in the RET group compared to the SA group, whereas ActRIIB protein expression in the femur showed no obvious differences among groups. Overall, the observed changes in IGF-1 and myostatin expression and their downstream targets may be involved in musculoskeletal preservation during hibernation in Daurian ground squirrels.


Assuntos
Hibernação , Fator de Crescimento Insulin-Like I , Músculo Esquelético , Miostatina , Sciuridae , Animais , Miostatina/metabolismo , Miostatina/genética , Hibernação/fisiologia , Sciuridae/fisiologia , Sciuridae/metabolismo , Músculo Esquelético/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fosforilação , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 1/genética , Osso e Ossos/metabolismo , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fêmur/metabolismo
5.
PLoS One ; 19(8): e0307551, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39197002

RESUMO

The effect of hibernation on cognitive capacities of individuals is not fully understood, as studies provide conflicting results. Most studies focus on behavioural observations without taking the physiological state of individuals to account. To mechanistically understand the effect of hibernation on the brain, physiological parameters need to be included. The implantation of bio-loggers can provide insights on i.e. body temperature without further manipulation of the animals. Surgeries and anaesthesia, however, can harm animals' health and cause cognitive dysfunction, potentially biasing data collected through bio-loggers. We investigated the effects of bio-logger implantation surgery on cognitive performance and learning, controlling for animal and study design characteristics. First, juvenile dormice successfully learned to solve a spatial cognition task using a vertical maze. Distance, transitions, velocity, and duration were measured as indicators for performance. After training, bio-loggers were implanted intra-abdominally under general anaesthesia. Animals were re-tested in the maze two weeks after. We found no effect of bio-logger implantation and surgery on performance. This study is the first to show spatial cognition learning in edible dormice and provides a full description of the peri-anaesthetic management and a protocol for bio-logger implantation surgery in dormice. Importantly, measures were taken to mitigate common anaesthetic complications that could lead to post-operative cognitive dysfunction and influence animal behaviour. By pairing physiological measurements through bio-logger implantation with behaviour and cognition measurements, future research will significantly advance the understanding on mechanisms of learning and behaviour.


Assuntos
Anestesia Geral , Cognição , Hibernação , Animais , Cognição/fisiologia , Hibernação/fisiologia , Aprendizagem em Labirinto , Aprendizagem Espacial , Masculino
6.
PLoS Pathog ; 20(8): e1012342, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39207947

RESUMO

The emergence of white-nose syndrome (WNS) in North America has resulted in mass mortalities of hibernating bats and total extirpation of local populations. The need to mitigate this disease has stirred a significant body of research to understand its pathogenesis. Pseudogymnoascus destructans, the causative agent of WNS, is a psychrophilic (cold-loving) fungus that resides within the class Leotiomycetes, which contains mainly plant pathogens and is unrelated to other consequential pathogens of animals. In this review, we revisit the unique biology of hibernating bats and P. destructans and provide an updated analysis of the stages and mechanisms of WNS progression. The extreme life history of hibernating bats, the psychrophilic nature of P. destructans, and its evolutionary distance from other well-characterized animal-infecting fungi translate into unique host-pathogen interactions, many of them yet to be discovered.


Assuntos
Ascomicetos , Quirópteros , Hibernação , Quirópteros/microbiologia , Animais , Ascomicetos/patogenicidade , Hibernação/fisiologia , Interações Hospedeiro-Patógeno , Micoses/veterinária , Micoses/microbiologia , Dermatomicoses/veterinária , Dermatomicoses/microbiologia , Dermatomicoses/patologia , Pele/microbiologia , Pele/patologia , Brancos
7.
Appl Environ Microbiol ; 90(8): e0069324, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39058040

RESUMO

Symbiotic microorganisms that reside on the host skin serve as the primary defense against pathogens in vertebrates. Specifically, the skin microbiome of bats may play a crucial role in providing resistance against Pseudogymnoascus destructans (Pd), the pathogen causing white-nose syndrome. However, the epidermis symbiotic microbiome and its specific role in resisting Pd in highly resistant bats in Asia are still not well understood. In this study, we collected and characterized skin microbiota samples of 19 Myotis pilosus in China and explored the differences between Pd-positive and negative individuals. We identified inhibitory effects of these bacteria through cultivation methods. Our results revealed that the Simpson diversity index of the skin microbiota for positive individuals was significantly lower than that of negative individuals, and the relative abundance of Pseudomonas was significantly higher in positive bats. Regardless of whether individuals were positive or negative for Pd, the relative abundance of potentially antifungal genera in skin microbiota was high. Moreover, we successfully isolated 165 microbes from bat skin and 41 isolates from positive individuals able to inhibit Pd growth compared to only 12 isolates from negative individuals. A total of 10 genera of Pd-inhibiting bacteria were screened, among which the genera Algoriella, Glutamicibacter, and Psychrobacter were newly discovered as Pd-inhibiting genera. These Pd-inhibiting bacteria metabolized a variety of volatile compounds, including dimethyl trisulfide, dimethyl disulfide, propylene sulfide, 2-undecanone, and 2-nonanone, which were able to completely inhibit Pd growth at low concentrations.IMPORTANCERecently, white-nose syndrome has caused the deaths of millions of hibernating bats, even threatening some with regional extinction. Bats in China with high resistance to Pseudogymnoascus destructans can provide a powerful reference for studying the management of white-nose syndrome and understanding the bats against the pathogen's intrinsic mechanisms. This study sheds light on the crucial role of host symbiotic skin microorganisms in resistance to pathogenic fungi and highlights the potential for harnessing natural defense mechanisms for the prevention and treatment of white-nose syndrome. In addition, this may also provide promising candidates for the development of bioinsecticides and fungicides that offer new avenues for addressing fungal diseases in wildlife and agricultural environments.


Assuntos
Ascomicetos , Bactérias , Quirópteros , Hibernação , Microbiota , Pele , Quirópteros/microbiologia , Animais , Pele/microbiologia , Ascomicetos/isolamento & purificação , Ascomicetos/fisiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , China , Simbiose
8.
J Therm Biol ; 123: 103909, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39084175

RESUMO

Fine-scale variation in microclimates between habitats may impact energy consumption for the organisms that inhabit them. This may be particularly important for sedentary species or those unable to change habitats for long periods, such as hibernators. Low ambient temperatures were traditionally thought key to microclimatic selection for hibernation locations, but recent research suggests that other factors may contribute or exceed ambient temperature in importance. We aimed to characterise microclimates at hibernacula of wild hibernating hazel dormice Muscardinus avellanarius, and test how these microclimates differ to those at locations without hibernacula using a microclimatic modelling approach. Dormice hibernated in areas with warmer soil temperatures and lower variability in humidity and relative shortwave radiation. These results add to the growing body of evidence that low ambient temperatures may not be the primary driver of hibernation microclimate selection, although temperature is still likely to play an important role. We also found that ambient temperatures measured at the microclimatic level were substantially buffered compared to point samples taken at the nearest weather station (∼1.6 km away), highlighting the importance of considering microclimates in wildlife conservation in the face of future environmental change.


Assuntos
Hibernação , Microclima , Animais , Hibernação/fisiologia , Estações do Ano , Temperatura , Myoxidae/fisiologia , Comportamento de Nidação , Ecossistema
9.
J Therm Biol ; 123: 103913, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39002254

RESUMO

Oxidative stress is thought to be one of the main causes of ageing as it progressively damages cell components throughout life, eventually causing cellular failure and apoptosis. In many organisms, telomeres shorten throughout life under the effect of, amongst other factors, oxidative stress, and are therefore commonly used as marker of biological ageing. However, hibernators, which are regularly exposed to acute oxidative stress when rewarming from torpor, are unexpectedly long-lived. In this review, we explore the causes of oxidative stress associated with hibernation and its impact on telomere dynamics in different taxa, focussing on hibernating rodents. We then speculate on the adaptive mechanisms of hibernators to compensate for the effects of oxidative stress, which may explain their increased longevity. Because winter hibernation appears to be associated with high oxidative stress, hibernators, particularly rodents, may periodically invest in repair mechanisms and antioxidant defences, resulting in seasonal variations in telomere lengths. This research shows how species with a slow life-history strategy deal with large changes in oxidative stress, unifying evolutionary and physiological theories of ageing. Because of the marked seasonal variation in telomere length, we also draw attention when using telomeres as markers for biological aging in seasonal heterotherms and possibly in other highly seasonal species.


Assuntos
Hibernação , Estresse Oxidativo , Estações do Ano , Telômero , Animais , Telômero/genética , Homeostase do Telômero , Encurtamento do Telômero , Envelhecimento/genética
10.
Sci Transl Med ; 16(758): eadg3894, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083588

RESUMO

Patients receiving mechanical ventilation in the intensive care unit (ICU) frequently develop contractile weakness of the diaphragm. Consequently, they may experience difficulty weaning from mechanical ventilation, which increases mortality and poses a high economic burden. Because of a lack of knowledge regarding the molecular changes in the diaphragm, no treatment is currently available to improve diaphragm contractility. We compared diaphragm biopsies from ventilated ICU patients (N = 54) to those of non-ICU patients undergoing thoracic surgery (N = 27). By integrating data from myofiber force measurements, x-ray diffraction experiments, and biochemical assays with clinical data, we found that in myofibers isolated from the diaphragm of ventilated ICU patients, myosin is trapped in an energy-sparing, super-relaxed state, which impairs the binding of myosin to actin during diaphragm contraction. Studies on quadriceps biopsies of ICU patients and on the diaphragm of previously healthy mechanically ventilated rats suggested that the super-relaxed myosins are specific to the diaphragm and not a result of critical illness. Exposing slow- and fast-twitch myofibers isolated from the diaphragm biopsies to small-molecule compounds activating troponin restored contractile force in vitro. These findings support the continued development of drugs that target sarcomere proteins to increase the calcium sensitivity of myofibers for the treatment of ICU-acquired diaphragm weakness.


Assuntos
Diafragma , Contração Muscular , Miosinas , Respiração Artificial , Músculos Respiratórios , Humanos , Animais , Miosinas/metabolismo , Diafragma/metabolismo , Diafragma/fisiopatologia , Músculos Respiratórios/metabolismo , Ratos , Masculino , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Feminino , Idoso , Hibernação/fisiologia , Actinas/metabolismo
11.
Sci Total Environ ; 948: 174852, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39029756

RESUMO

Bumblebees and other key pollinators are experiencing global declines, a phenomenon driven by multiple environmental stressors, including pesticide exposure. While bumblebee queens spend most of their life hibernating underground, no study to date has examined how exposure to pesticide-contaminated soils might affect bumblebee queens during this solitary phase of their lifecycle. We exposed Bombus impatiens queens (n = 303) to soil treated with field-realistic concentrations of two diamide insecticides (chlorantraniliprole and cyantraniliprole) and two fungicides (boscalid and difenoconazole), alone or combined, during a 30-week hibernation period. We found that exposure to boscalid residues in soil doubled the likelihood of queens surviving through the colony initiation period (after successful hibernation) and laying eggs. Our data also revealed complex interactions between pesticide exposure and queen body mass on aspects of colony founding. Among others, exposure to cyantraniliprole led to lethal and sublethal post-hibernation effects that were dependent on queen size, with larger queens showing higher mortality rates, delayed emergence of their first brood, and producing smaller workers. Our results show that effects of pesticide exposure depend on intrinsic traits of bumblebee queen physiology and challenge our understanding of how bees respond to pesticides under environmentally realistic exposure scenarios.


Assuntos
Hibernação , Resíduos de Praguicidas , Poluentes do Solo , Animais , Abelhas/fisiologia , Abelhas/efeitos dos fármacos , Resíduos de Praguicidas/análise , Feminino , Hibernação/fisiologia , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , ortoaminobenzoatos/toxicidade , Inseticidas/toxicidade , Inseticidas/análise , Compostos de Bifenilo , Fungicidas Industriais/toxicidade , Pirazóis/toxicidade , Triazóis/toxicidade , Tamanho Corporal/efeitos dos fármacos , Dioxolanos , Niacinamida/análogos & derivados
12.
PLoS One ; 19(7): e0306537, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39083476

RESUMO

In wild brown bears, likely factors triggering hibernation response to harsh environmental conditions are temperature, photoperiod, and food resources availability. In fact, constantly fed captive brown bears are described as skipping hibernation being active all year-round. Is the hibernation response so flexible and subordinate to contingencies, or else is an adaptation that, if dismissed, may negatively impact on bear well-being? This study investigates the potential hibernation response in captive brown bears under unvaried management conditions using an integrative approach simultaneously analyzing multiple animal-based variables together with environmental covariates. Data from a mid-latitude zoo revealed distinct behavioral, fecal glucocorticoids, and body condition score seasonal fluctuations, resembling natural hibernation cycles, despite constant food access. Environmental variables like photoperiod and visitor numbers significantly influenced activity levels. Bears exhibited behaviors indicative of hyperphagia and fall transition, such as appetitive feeding and denning behaviors. Hormonal analyses revealed high fecal cortisol metabolites levels during hyperphagia, suggesting physiological responses to seasonal changes. Findings underscore the importance of environmental cues and food availability in shaping zoo bear behavior and physiology. Considering that the hibernating vs. non-hibernating description might represent an oversimplification, management strategies should deal with captive bear potential need to freely express their adaptive predispositions by accommodating their natural behaviors, such as providing denning spots and adjusting diet composition as soon as typical hyperphagic and predenning behaviors emerge, ultimately enhancing their well-being.


Assuntos
Animais de Zoológico , Hibernação , Estações do Ano , Ursidae , Animais , Ursidae/fisiologia , Hibernação/fisiologia , Animais de Zoológico/fisiologia , Masculino , Feminino , Hidrocortisona/metabolismo , Hidrocortisona/análise , Comportamento Animal/fisiologia , Sinais (Psicologia) , Bem-Estar do Animal , Fotoperíodo , Fezes/química , Meio Ambiente
13.
Oecologia ; 205(3-4): 497-513, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38981874

RESUMO

Demography of herbivorous mammal populations may be affected by changes in predation, population density, harvesting, and climate. Whereas numerous studies have focused on the effect of single environmental variables on individual demographic processes, attempts to integrate the consequences of several environmental variables on numerous functional traits and demographic rates are rare. Over a 32-year period, we examined how forage availability (vegetation assessed through NDVI) and population density affected the functional traits and demographic rates of a population of Columbian ground squirrels (Urocitellus columbianus), a herbivorous hibernating rodent. We focused on mean population phenology, body mass, breeding success, and survival. We found a negative effect of population density on demographic rates, including on breeding success and pup and adult survival to the next year. We found diverging effects of vegetation phenology on demographic rates: positive effects of a later start of the growing season on adult and yearling female survival, and juvenile survival, but no clear effect on male survival. Interestingly, neither population density nor vegetation affected population phenology or body condition in the following year. Vegetative growth rate had a positive influence on female mass gain (somatic investment) over a season, but both vegetative growth rate and biomass, surprisingly, had negative effects on the survival of young through their first hibernation. Thus, ground squirrels appeared to benefit more from later timing of vegetation than increases in vegetative biomass per se. Our study provides evidence for complex ecological effects of vegetation and population density on functional traits and demographic rates of small mammal populations.


Assuntos
Herbivoria , Hibernação , Densidade Demográfica , Animais , Sciuridae/fisiologia , Estações do Ano , Dinâmica Populacional , Mamíferos , Feminino , Masculino , Ecossistema
14.
Nat Commun ; 15(1): 5803, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987241

RESUMO

Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5-7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24-48-h periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger during IBAs. These squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons exhibit reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.


Assuntos
Anorexia , Grelina , Hibernação , Hipotálamo , Sciuridae , Animais , Hibernação/fisiologia , Sciuridae/fisiologia , Anorexia/fisiopatologia , Anorexia/metabolismo , Hipotálamo/metabolismo , Grelina/metabolismo , Grelina/deficiência , Leptina/deficiência , Leptina/metabolismo , Núcleo Arqueado do Hipotálamo/metabolismo , Neurônios/metabolismo , Neurônios/fisiologia , Masculino , Hormônios Tireóideos/metabolismo , Nível de Alerta/fisiologia , Feminino , Estações do Ano , Comportamento Alimentar/fisiologia
15.
Science ; 385(6705): 194-200, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38991070

RESUMO

Millions of hibernating bats across North America have died from white-nose syndrome (WNS), an emerging disease caused by a psychrophilic (cold-loving) fungus, Pseudogymnoascus destructans, that invades their skin. Mechanisms of P. destructans invasion of bat epidermis remain obscure. Guided by our in vivo observations, we modeled hibernation with a newly generated little brown bat (Myotis lucifugus) keratinocyte cell line. We uncovered the stealth intracellular lifestyle of P. destructans, which inhibits apoptosis of keratinocytes and spreads through the cells by two epidermal growth factor receptor (EGFR)-dependent mechanisms: active penetration during torpor and induced endocytosis during arousal. Melanin of endocytosed P. destructans blocks endolysosomal maturation, facilitating P. destructans survival and germination after return to torpor. Blockade of EGFR aborts P. destructans entry into keratinocytes.


Assuntos
Nível de Alerta , Ascomicetos , Quirópteros , Receptores ErbB , Hibernação , Queratinócitos , Animais , Apoptose , Ascomicetos/fisiologia , Ascomicetos/patogenicidade , Linhagem Celular , Quirópteros/microbiologia , Quirópteros/fisiologia , Endocitose , Receptores ErbB/metabolismo , Queratinócitos/microbiologia , Melaninas/metabolismo
16.
Science ; 385(6705): 142-143, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38991085

RESUMO

A fungus uses different cell entry strategies, depending on its host's hibernation status.


Assuntos
Ascomicetos , Quirópteros , Hibernação , Interações Hospedeiro-Patógeno , Animais , Quirópteros/microbiologia , Quirópteros/fisiologia , Ascomicetos/patogenicidade
17.
Artigo em Inglês | MEDLINE | ID: mdl-39032767

RESUMO

Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology.


Assuntos
Apoptose , Autofagia , Hibernação , Dinâmica Mitocondrial , Sciuridae , Testículo , Animais , Masculino , Sciuridae/fisiologia , Sciuridae/metabolismo , Hibernação/fisiologia , Testículo/metabolismo , Testículo/fisiologia , Autofagia/fisiologia , Mitocôndrias/metabolismo , Estações do Ano , Testosterona/metabolismo , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo
18.
Sci Rep ; 14(1): 13496, 2024 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866865

RESUMO

Estimating population changes of bats is important for their conservation. Population estimates of hibernating bats are often calculated by researchers entering hibernacula to count bats; however, the disturbance caused by these surveys can cause bats to arouse unnaturally, fly, and lose body mass. We conducted 17 hibernacula surveys in 9 caves from 2013 to 2018 and used acoustic detectors to document cave-exiting bats the night following our surveys. We predicted that cave-exiting flights (i.e., bats flying out and then back into caves) of Townsend's big-eared bats (Corynorhinus townsendii) and western small-footed myotis (Myotis ciliolabrum) would be higher the night following hibernacula surveys than on nights following no surveys. Those two species, however, did not fly out of caves more than predicted the night following 82% of surveys. Nonetheless, the activity of bats flying out of caves following surveys was related to a disturbance factor (i.e., number of researchers × total time in a cave). We produced a parsimonious model for predicting the probability of Townsend's big-eared bats flying out of caves as a function of disturbance factor and ambient temperature. That model can be used to help biologists plan for the number of researchers, and the length of time those individuals are in a cave to minimize disturbing bats.


Assuntos
Cavernas , Quirópteros , Hibernação , Animais , Quirópteros/fisiologia , Voo Animal/fisiologia
19.
Physiol Genomics ; 56(8): 555-566, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38881427

RESUMO

Thirteen-lined ground squirrels (TLGSs) are obligate hibernators that cycle between torpor (low metabolic rate and body temperature) and interbout euthermia (IBE; typical euthermic body temperature and metabolism) from late autumn to spring. Many physiological changes occur throughout hibernation, including a reduction in liver mitochondrial metabolism during torpor, which is reversed during arousal to interbout euthermia. Nuclear-encoded microRNA (miRNA, small posttranscriptional regulator molecules) differ in abundance throughout TLGS hibernation and have been shown to regulate mitochondrial gene expression in mammalian cell culture (where they are referred to as mitomiRs). This study characterized differences in mitomiR profiles from TLGS liver mitochondria isolated during summer, torpor, and IBE, and predicted their mitochondrial targets. Using small RNA sequencing, differentially abundant mitomiRs were identified between hibernation states, and using quantitative PCR analysis, we quantified the expression of predicted mitochondrial mRNA targets. Most differences in mitomiR abundances were seasonal (i.e., between summer and winter) with only one mitomiR differentially abundant between IBE and torpor. Multiple factor analysis (MFA) revealed three clusters divided by hibernation states, where clustering was predominantly driven by mitomiR abundances. Nine of these differentially abundant mitomiRs had predicted mitochondrial RNA targets, including subunits of electron transfer system complexes I and IV, 12S rRNA, and two tRNAs. Overall, mitomiRs were predicted to suppress the expression of their mitochondrial targets and may have some involvement in regulating protein translation in mitochondria. This study found differences in mitomiR abundances between seasons and hibernation states of TLGS and suggests potential mechanisms for regulating the mitochondrial electron transfer system.NEW & NOTEWORTHY During the hibernation season, thirteen-lined ground squirrels periodically increase metabolism remarkably between torpor and interbout euthermia (IBE). This process involves rapid reactivation of mitochondrial respiration. We predicted that mitochondrial microRNA (mitomiRs) might be altered during this response. We found that the abundance of 38 liver mitomiRs differs based on hibernation state (summer, IBE, and torpor). Small RNA sequencing identified mitomiR profiles, including some mitomiRs that are predicted to bind to mitochondrial RNAs.


Assuntos
Hibernação , MicroRNAs , Sciuridae , Animais , Sciuridae/genética , Hibernação/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Estações do Ano , Torpor/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/genética
20.
Proc Biol Sci ; 291(2025): 20240266, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38920109

RESUMO

Climate change has physiological consequences on organisms, ecosystems and human societies, surpassing the pace of organismal adaptation. Hibernating mammals are particularly vulnerable as winter survival is determined by short-term physiological changes triggered by temperature. In these animals, winter temperatures cannot surpass a certain threshold, above which hibernators arouse from torpor, increasing several fold their energy needs when food is unavailable. Here, we parameterized a numerical model predicting energy consumption in heterothermic species and modelled winter survival at different climate change scenarios. As a model species, we used the arboreal marsupial monito del monte (genus Dromiciops), which is recognized as one of the few South American hibernators. We modelled four climate change scenarios (from optimistic to pessimistic) based on IPCC projections, predicting that northern and coastal populations (Dromiciops bozinovici) will decline because the minimum number of cold days needed to survive the winter will not be attained. These populations are also the most affected by habitat fragmentation and changes in land use. Conversely, Andean and other highland populations, in cooler environments, are predicted to persist and thrive. Given the widespread presence of hibernating mammals around the world, models based on simple physiological parameters, such as this one, are becoming essential for predicting species responses to warming in the short term.


Assuntos
Mudança Climática , Hibernação , Marsupiais , Estações do Ano , Animais , Marsupiais/fisiologia , Dinâmica Populacional , Modelos Biológicos , Ecossistema , Metabolismo Energético
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