RESUMEN
Whether the forelimb-digging apparatus of tooth-digging subterranean mammals has similar levels of specialization as compared to scratch-diggers is still unknown. We assessed the scapular morphology and forelimb musculature of all four solitary African mole rats (Bathyergidae): two scratch-diggers, Bathyergus suillus and Bathyergus janetta, and two chisel-tooth diggers, Heliophobius argenteocinereus and Georychus capensis. Remarkable differences were detected: Bathyergus have more robust neck, shoulder, and forearm muscles as compared to the other genera. Some muscles in Bathyergus were also fused and often showing wider attachment areas to bones, which correlate well with its more robust and larger scapula, and its wider and medially oriented olecranon. This suggests that shoulder, elbow, and wrist work in synergy in Bathyergus for generating greater out-forces and that the scapula and proximal ulna play fundamental roles as pivots to maximize and accommodate specialized muscles for better (i) glenohumeral and scapular stabilization, (ii) powerful shoulder flexion, (iii) extension of the elbow and (iv) flexion of the manus and digits. Moreover, although all bathyergids showed a similar set of muscles, Heliophobius lacked the m. tensor fasciae antebrachii (aiding with elbow extension and humeral retraction), and Heliophobius and Georychus lacked the m. articularis humeri (aiding with humeral adduction), indicating deeper morphogenetic differences among digging groups and suggesting a relatively less specialized scratch-digging ability. Nevertheless, Heliophobius and Bathyergus shared some similar adaptations allowing scratch-digging. Our results provide new information about the morphological divergence within this family associated with the specialization to distinct functions and digging behaviors, thus contributing to understand the mosaic of adaptations emerging in phylogenetically and ecologically closer subterranean taxa. This and previous anatomical studies on the Bathyergidae will provide researchers with a substantial basis on the form and function of the musculoskeletal system for future kinematic investigations of digging behavior, as well as to define potential indicators of scratch-digging ability.
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Miembro Anterior , Animales , Miembro Anterior/anatomía & histología , Miembro Anterior/fisiología , Músculo Esquelético/anatomía & histología , Músculo Esquelético/fisiología , Ratas Topo/anatomía & histología , Ratas Topo/fisiología , Sistema Musculoesquelético/anatomía & histología , Escápula/anatomía & histología , Escápula/fisiologíaRESUMEN
Naked mole-rats (Heterocephalus glaber) live in large colonies with one breeding female (queen), one to three breeding males (BMs) and the remainder are non-reproductive subordinates. The animals have a linear dominance rank with the breeders at the top of the hierarchy. We investigated how dominance rank in naked mole-rats differs with exploration (the propensity to explore a novel environment) and related endocrine markers. Exploration behaviour, faecal progestagen metabolite (fPM), faecal glucocorticoid metabolite (fGCM), faecal androgen metabolite (fAM) and plasma prolactin concentrations were quantified in breeding, high-, middle- and low-ranked females and males from five naked mole-rat colonies. There were no significant differences between the dominance rank and exploration behaviour. Interestingly, the queens and high-ranking females had higher fGCM and fAM concentrations compared with middle- and low-ranked females. The queens had significantly higher fPM concentrations than all other ranked females, since they are responsible for procreation. In the males, the BMs had higher fGCM concentrations compared with high- and low-ranked males. In addition, BMs and middle-ranking males had overall higher prolactin levels than all other ranked males, which could be linked to cooperative care. Overall, the results suggest that physiological reproductive suppression is linked to high dominance rank.
Asunto(s)
Andrógenos , Heces , Ratas Topo , Prolactina , Predominio Social , Animales , Masculino , Femenino , Prolactina/metabolismo , Prolactina/sangre , Heces/química , Ratas Topo/fisiología , Andrógenos/metabolismo , Andrógenos/sangre , Glucocorticoides/metabolismo , Conducta Exploratoria , Progestinas/metabolismoAsunto(s)
Hipoxia , Ratas Topo , Animales , Ratas Topo/fisiología , Hipoxia/fisiopatología , Estrés Fisiológico , Corazón/fisiologíaRESUMEN
The search for solutions to the vagaries of aging has, historically, been akin to searching at night in the bright light under street lamps by utilizing the few preexisting and well-established animal model systems. Throughout my career as a comparative biologist, I have ventured into the darkness across 4 continents and studied over 150 different animal species, many of which have evolved remarkable adaptations to survive on the harsh and rugged fitness landscape that exists outside of the laboratory setting. In this Fellows Forum, I will discuss the main focus of my research for the last 25 years and dig deeply into the biology of the preternaturally long-lived naked mole-rat that makes it an ideal model system for the characterization of successful strategies to combat aging.
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Envejecimiento , Longevidad , Ratas Topo , Animales , Envejecimiento/fisiología , Longevidad/fisiología , Modelos Animales , Ratas Topo/fisiologíaRESUMEN
Naked mole-rats (NMRs) are among the most hypoxia-tolerant mammals and metabolize only carbohydrates in hypoxia. Glucose is the primary building block of dietary carbohydrates, but how blood glucose is regulated during hypoxia has not been explored in NMRs. We hypothesized that NMRs mobilize glucose stores to support anaerobic energy metabolism in hypoxia. To test this, we treated newborn, juvenile and adult (subordinate and queen) NMRs in normoxia (21% O2) or hypoxia (7, 5 or 3% O2), while measuring metabolic rate, body temperature and blood [glucose]. We also challenged animals with glucose, insulin or insulin-like growth factor-1 (IGF-1) injections and measured the rate of glucose clearance in normoxia and hypoxia. We found that: (1) blood [glucose] increases in moderate hypoxia in queens and pups, but only in severe hypoxia in adult subordinates and juveniles; (2) glucose tolerance is similar between developmental stages in normoxia, but glucose clearance times are 2- to 3-fold longer in juveniles and subordinates than in queens or pups in hypoxia; and (3) reoxygenation accelerates glucose clearance in hypoxic subordinate adults. Mechanistically, (4) insulin and IGF-1 reduce blood [glucose] in subordinates in both normoxia but only IGF-1 impacts blood [glucose] in hypoxic queens. Our results indicate that insulin signaling is impaired by hypoxia in NMRs, but that queens utilize IGF-1 to overcome this limitation and effectively regulate blood glucose in hypoxia. This suggests that sexual maturation impacts blood glucose handling in hypoxic NMR queens, which may allow queens to spend longer periods of time in hypoxic nest chambers.
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Glucemia , Homeostasis , Hipoxia , Ratas Topo , Animales , Ratas Topo/fisiología , Femenino , Glucemia/metabolismo , Hipoxia/metabolismo , Masculino , Insulina/metabolismo , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Glucosa/metabolismoRESUMEN
Cancer is an inevitable collateral problem inherent in the evolution of multicellular organisms, which appeared at the end of the Precambrian. Faced to this constraint, a range of diverse anticancer defenses has evolved across the animal kingdom. Today, investigating how animal organisms, especially those of large size and long lifespan, manage cancer-related issues has both fundamental and applied outcomes, as it could inspire strategies for preventing or treating human cancers. In this article, we begin by presenting the conceptual framework for understanding evolutionary theories regarding the development of anti-cancer defenses. We then present a number of examples that have been extensively studied in recent years, including naked mole rats, elephants, whales, placozoa, xenarthras (such as sloths, armadillos and anteaters) and bats. The contributions of comparative genomics to understanding evolutionary convergences are also discussed. Finally, we emphasize that natural selection has also favored anti-cancer adaptations aimed at avoiding mutagenic environments, for example by maximizing immediate reproductive efforts in the event of cancer. Exploring these adaptive solutions holds promise for identifying novel approaches to improve human health.
Title: Évolution de la résistance au cancer dans le monde animal. Abstract: Le cancer est un dommage collatéral inévitable inhérent à l'évolution des organismes multicellulaires, apparus à la fin du Précambrien. L'exploration de la manière dont les animaux, en particulier ceux de grande taille et de longue durée de vie, font face au cancer, comporte des enjeux à la fois fondamentaux et appliqués. Dans cet article, nous commençons par présenter le cadre conceptuel nécessaire pour comprendre les théories qui traitent de l'évolution des défenses anti-cancéreuses. Nous présentons ensuite un certain nombre d'exemples, notamment les rats-taupes nus, les éléphants, les baleines, les xénarthres (paresseux, tatous et fourmiliers), les chauves-souris et les placozoaires1. Les contributions de la génomique comparative à la compréhension des convergences évolutives sont également abordées. Enfin, nous indiquons que la sélection naturelle a également favorisé des adaptations visant à éviter les zones mutagènes, par exemple, ou à maximiser l'effort de reproduction immédiat en cas de cancer. L'exploration de ces solutions, intéressante conceptuellement, pourrait aussi permettre d'envisager de nouvelles approches thérapeutiques pour la santé humaine.
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Evolución Biológica , Neoplasias , Animales , Neoplasias/genética , Neoplasias/patología , Humanos , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/fisiología , Selección Genética , Ratas Topo/fisiología , Ratas Topo/genética , Elefantes/genéticaRESUMEN
Naked mole-rats (NMRs) are best known for their extreme longevity and cancer resistance, suggesting that their immune system might have evolved to facilitate these phenotypes. Natural killer (NK) and T cells have evolved to detect and destroy cells infected with pathogens and to provide an early response to malignancies. While it is known that NMRs lack NK cells, likely lost during evolution, little is known about their T-cell subsets in terms of the evolution of the genes that regulate their function, their clonotypic diversity, and the thymus where they mature. Here we find, using single-cell transcriptomics, that NMRs have a large circulating population of γδT cells, which in mice and humans mostly reside in peripheral tissues and induce anti-cancer cytotoxicity. Using single-cell-T-cell-receptor sequencing, we find that a cytotoxic γδT-cell subset of NMRs harbors a dominant clonotype, and that their conventional CD8 αßT cells exhibit modest clonotypic diversity. Consistently, perinatal NMR thymuses are considerably smaller than those of mice yet follow similar involution progression. Our findings suggest that NMRs have evolved under a relaxed intracellular pathogenic selective pressure that may have allowed cancer resistance and longevity to become stronger targets of selection to which the immune system has responded by utilizing γδT cells.
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Longevidad , Neoplasias , Humanos , Animales , Ratones , Longevidad/fisiología , Neoplasias/genética , Subgrupos de Linfocitos T , Células Asesinas Naturales , Ratas Topo/fisiologíaRESUMEN
African mole-rats live in self-dug burrow systems under hypoxic and hypercapnic conditions. Adaptations to hypoxia include suppression of resting metabolic rate (RMR) and core body temperature (Tb). Because the thyroid hormones (THs) thyroxine (T4) and triiodothyronine (T3) are positive regulators of RMR and Tb, we hypothesized that serum TH concentrations would also be downregulated under hypoxic conditions. To test this hypothesis, we kept Ansell's mole-rats (Fukomys anselli) in terraria filled with soil in which they were allowed to construct underground burrows to achieve chronic intermittent hypoxia and hypercapnia. The animals stayed in these hypoxic and hypercapnic burrows voluntarily, although given the choice to stay aboveground. We collected blood samples before and after treatment to measure serum T4 and T3 concentrations as well as hematological parameters. The free fraction of the transcriptionally-active T3 was significantly decreased after treatment, indicating that cellular TH signaling was downregulated via peripheral mechanisms, consistent with the assumption that aerobic metabolism is downregulated under hypoxic conditions. Furthermore, we found that hematocrit and hemoglobin concentrations were also downregulated after treatment, suggesting that oxygen demand decreases under hypoxia, presumably due to the metabolic shift towards anaerobic metabolism. Taken together, we have identified a potential upstream regulator of physiological adaptations to hypoxia in these highly hypoxia-tolerant animals.
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Ratas Topo , Triyodotironina , Animales , Ratas Topo/fisiología , Hipercapnia , Regulación hacia Abajo , Hematócrito , HipoxiaRESUMEN
Fossorial Damaraland mole-rats (Fukomys damarensis) mount a robust hypoxic metabolic response (HMR) but a blunted hypoxic ventilatory response (HVR) to acute hypoxia. Although these reflex physiological responses have been described previously, the underlying signalling pathways are entirely unknown. Of particular interest are contributions from γ-aminobutyric acid (GABA), which is the primary inhibitory neurotransmitter in the nervous system of most adult mammals, and adenosine, the accumulation of which increases during hypoxia as a breakdown product of ATP. Therefore, we hypothesized that GABAergic and/or adenosinergic signalling contributes to the blunted HVR and robust HMR in Damaraland mole-rats. To test this hypothesis, we injected adult animals with saline alone (controls), or 100â mgâ kg-1 aminophylline or 1â mgâ kg-1 bicuculline, to block adenosine or GABAA receptors, respectively. We then used respirometry, plethysmography and thermal RFID probes to non-invasively measure metabolic, ventilator and thermoregulatory responses, respectively, to acute hypoxia (1â h in 5 or 7% O2) in awake and freely behaving animals. We found that bicuculline had relatively minor effects on metabolism and thermoregulation but sensitized ventilation such that the HVR became manifest at 7% instead of 5% O2 and was greater in magnitude. Aminophylline increased metabolic rate, ventilation and body temperature in normoxia, and augmented the HMR and HVR. Taken together, these findings indicate that adenosinergic and GABAergic signalling play important roles in mediating the robust HMR and blunted HVR in Damaraland mole-rats.
Asunto(s)
Adenosina , Aminofilina , Animales , Bicuculina/farmacología , Adenosina/farmacología , Ratas Topo/fisiología , Hipoxia/metabolismo , Ácido gamma-AminobutíricoRESUMEN
Hypoxemia from exposure to intermittent and/or acute environmental hypoxia (lower oxygen concentration) is a severe stressor for many animal species. The response to hypoxia of the hypothalamic-pituitary-adrenal axis (HPA-axis), which culminates in the release of glucocorticoids, has been well-studied in hypoxia-intolerant surface-dwelling mammals. Several group-living (social) subterranean species, including most African mole-rats, are hypoxia-tolerant, likely due to regular exposure to intermittent hypoxia in their underground burrows. Conversely, solitary mole-rat species, lack many adaptive mechanisms, making them less hypoxia-tolerant than the social genera. To date, the release of glucocorticoids in response to hypoxia has not been measured in hypoxia-tolerant mammalian species. Consequently, this study exposed three social African mole-rat species and two solitary mole-rat species to normoxia, or acute hypoxia and then measured their respective plasma glucocorticoid (cortisol) concentrations. Social mole-rats had lower plasma cortisol concentrations under normoxia than the solitary genera. Furthermore, individuals of all three of the social mole-rat species exhibited significantly increased plasma cortisol concentrations after hypoxia, similar to those of hypoxia-intolerant surface-dwelling species. By contrast, individuals of the two solitary species had a reduced plasma cortisol response to acute hypoxia, possibly due to increased plasma cortisol under normoxia. If placed in perspective with other closely related surface-dwelling species, the regular exposure of the social African mole-rats to hypoxia may have reduced the basal levels of the components for the adaptive mechanisms associated with hypoxia exposure, including circulating cortisol levels. Similarly, the influence of body mass on plasma cortisol levels cannot be ignored. This study demonstrates that both hypoxia-tolerant rodents and hypoxia-intolerant terrestrial laboratory-bred rodents may possess similar HPA-axis responses from exposure to hypoxia. Further research is required to confirm the results from this pilot study and to further confirm how the cortisol concentrations may influence responses to hypoxia in African mole-rats.
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Hidrocortisona , Sistema Hipotálamo-Hipofisario , Animales , Proyectos Piloto , Sistema Hipófiso-Suprarrenal , Hipoxia , Ratas Topo/fisiología , GlucocorticoidesRESUMEN
Extreme environments are powerful drivers of physiological adaptation. Naked mole-rats offer an informative example of this relationship as they putatively encounter intermittent hypoxia and hypercapnia in their subterranean habitat. This has presumably driven the evolution of a suite of cellular and physiological adaptations that enable life in these conditions. Recently, my laboratory and others have begun to examine physiological responses to environmental hypoxia and hypercapnia in naked mole-rats, and the underlying cellular and molecular mechanisms that differentiate the responses of this species from those of other small mammals. Prominent among these adaptations are a robust hypoxic metabolic response and blunted ventilatory responses to hypoxia and hypercapnia. These responses are mediated in part by modifications to the central nervous system signaling pathways that sense and communicate changes in environmental gas levels and initiate and maintain downstream physiological responses. For example, naked mole-rats retain the signaling architecture necessary for "normal" ventilatory responses to hypoxia and hypercapnia; however, the underlying signaling pathways are muted, resulting in reduced, or even the absence of, sensitivity to otherwise powerful environmental stimuli. Herein, I discuss what we have learned about the manifestation and control of ventilatory and metabolic responses to hypoxia and hypercapnia in naked mole-rats. I also highlight areas where additional work is warranted and consider the implications of what we have learned for the ecophysiology of a species that thrives in conditions that are deleterious or lethal to most adult mammals.
Asunto(s)
Hipercapnia , Hipoxia , Animales , Hipoxia/metabolismo , Ratas Topo/fisiología , Adaptación Fisiológica , AclimataciónRESUMEN
African mole-rats are subterranean rodents inhabiting underground burrows. This habitat entails risks of overheating, hypoxia, and scarce food availability. Consequently, many subterranean species have evolved low basal metabolism and low body temperature, but the regulation of these traits at the molecular level were unknown. Measurements of serum thyroid hormone (TH) concentrations in African mole-rats have revealed a unique TH phenotype, which deviates from the typical mammalian pattern. Since THs are major regulators of metabolic rate and body temperature, we further characterised the TH system of two African mole-rat species, the naked mole-rat (Heterocephalus glaber) and the Ansell's mole-rat (Fukomys anselli) at the molecular level in a comparative approach involving the house mouse (Mus musculus) as a well-studied laboratory model in TH research. Most intriguingly, both mole-rat species had low iodide levels in the thyroid and naked mole-rats showed signs of thyroid gland hyperplasia. However, contrary to expectations, we found several species-specific differences in the TH systems of both mole-rat species, although ultimately resulting in similar serum TH concentrations. These findings indicate a possible convergent adaptation. Thus, our study adds to our knowledge for understanding adaptations to the subterranean habitat.
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Ratas Topo , Hormonas Tiroideas , Animales , Ratones , Ratas Topo/fisiología , Ecosistema , AclimataciónRESUMEN
Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-lived rodents with a maximum life span exceeding 37 years. They exhibit a delayed aging phenotype and resistance to age-related functional decline/diseases. Specifically, they do not display increased mortality with age, maintain several physiological functions until nearly the end of their lifetime, and rarely develop cancer and Alzheimer's disease. NMRs live in a hypoxic environment in underground colonies in East Africa and are highly tolerant of hypoxia. These unique characteristics of NMRs have attracted considerable interest from zoological and biomedical researchers. This review summarizes previous studies of the ecology, hypoxia tolerance, longevity/delayed aging, and cancer resistance of NMRs and discusses possible mechanisms contributing to their healthy aging. In addition, we discuss current issues and future perspectives to fully elucidate the mechanisms underlying delayed aging and resistance to age-related diseases in NMRs.
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Envejecimiento Saludable , Animales , Envejecimiento/genética , Longevidad/fisiología , Ratas Topo/fisiología , Hipoxia/veterinariaRESUMEN
Naked mole-rats are a long-lived rodent species (current lifespan >37 years) and an increasingly popular biomedical model. Naked mole-rats exhibit neuroplasticity across their long lifespan. Previous studies have begun to investigate their neurogenic patterns. Here, we test the hypothesis that neuronal maturation is extended in this long-lived rodent. We characterize cell proliferation and neuronal maturation in established rodent neurogenic regions over 12 months following seven days of consecutive BrdU injection. Given that naked mole-rats are eusocial (high reproductive skew where only a few socially-dominant individuals reproduce), we also looked at proliferation in brain regions relevant to the social-decision making network. Finally, we measured co-expression of EdU (newly-born cells), DCX (immature neuron marker), and NeuN (mature neuron marker) to assess the timeline of neuronal maturation in adult naked mole-rats. This work reaffirms the subventricular zone as the main source of adult cell proliferation and suggests conservation of the rostral migratory stream in this species. Our profiling of socially-relevant brain regions suggests that future work which manipulates environmental context can unveil how newly-born cells integrate into circuitry and facilitate adult neuroplasticity. We also find naked mole-rat neuronal maturation sits at the intersection of rodents and long-lived, non-rodent species: while neurons can mature by 3 weeks (rodent-like), most neurons mature at 5 months and hippocampal neurogenic levels are low (like long-lived species). These data establish a timeline for future investigations of longevity- and socially-related manipulations of naked mole-rat adult neurogenesis.
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Ratas Topo , Neurogénesis , Animales , Bromodesoxiuridina , Longevidad/fisiología , Ratas Topo/fisiología , Neuronas/fisiologíaRESUMEN
Life underground often leads to animals having specialized auditory systems to accommodate the constraints of acoustic transmission in tunnels. Despite living underground, naked mole-rats use a highly vocal communication system, implying that they rely on central auditory processing. However, little is known about these animals' central auditory system, and whether it follows a similar developmental time course as other rodents. Naked mole-rats show slowed development in the hippocampus suggesting they have altered brain development compared to other rodents. Here, we measured morphological characteristics and voltage-gated potassium channel Kv3.3 expression and protein levels at different key developmental time points (postnatal days 9, 14, 21 and adulthood) to determine whether the auditory brainstem (lateral superior olive and medial nucleus of the trapezoid body) develops similarly to two common auditory rodent model species: gerbils and mice. Additionally, we measured the hearing onset of naked mole-rats using auditory brainstem response recordings at the same developmental timepoints. In contrast with other work in naked mole-rats showing that they are highly divergent in many aspects of their physiology, we show that naked mole-rats have a similar hearing onset, between postnatal day (P) 9 and P14, to many other rodents. On the other hand, we show some developmental differences, such as a unique morphology and Kv3.3 protein levels in the brainstem.
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Tronco Encefálico , Ratas Topo , Animales , Percepción Auditiva/fisiología , Tronco Encefálico/anatomía & histología , Gerbillinae , Hipocampo , Ratones , Ratas Topo/fisiologíaRESUMEN
Evolutionary medicine has been a fast-growing field of biological research in the past decade. One of the strengths of evolutionary medicine is to use non-traditional model organisms which often exhibit unusual characteristics shaped by natural selection. Studying these unusual traits could provide valuable insight to understand biomedical questions, since natural selection likely discovers solutions to those complex biological problems. Because of many unusual traits, the naked mole-rat (NMR) has attracted attention from different research areas such as aging, cancer, and hypoxia- and hypercapnia-related disorders. However, such uniqueness of NMR physiology may sometimes make the translational study to human research difficult. Damaraland mole-rat (DMR) shares multiple characteristics in common with NMR, but shows higher degree of similarity with human in some aspects of their physiology. Research on DMR could therefore offer alternative insights and might bridge the gap between experimental findings from NMR to human biomedical research. In this review, we discuss studies of DMR as an extension of the current set of model organisms to help better understand different aspects of human biology and disease. We hope to encourage researchers to consider studying DMR together with NMR. By studying these two similar but evolutionarily distinct species, we can harvest the power of convergent evolution and avoid the potential biased conclusions based on life-history of a single species.
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Envejecimiento , Ratas Topo , Animales , Humanos , Ratas Topo/fisiologíaRESUMEN
The naked mole rat has unique biologic characteristics that include atypical inflammatory responses. Lipopolysaccharide induces inflammation which triggers brain centers controlling feeding, and behavior to result in "sick animal behavior". We characterized the bodyweight, locomotor, and other behavioral responses of this rodent to lipopolysaccharide administration. Lipopolysaccharide caused weight losses, which were not prevented by TAK 242. In the open field test, lipopolysaccharide did not depress locomotion, while urination, defecation, and activity freezing were rare. The animals exhibited walling but not rearing and fast backward movements that were unaffected by lipopolysaccharide. Failure to depress locomotion suggests either a unique immunity-brain crosstalk or motor responses/centers that tolerate depressive effects of inflammation. The absence of activity freezing and rarity of urination and defecation suggests that novel environments or lipopolysaccharide do not induce anxiety, or that anxiety is expressed differently in the animal. The absence of rearing could be due to the design of the animal's locomotor apparatus while fast backward movement could be a mechanism for quick escape from threats in the tunnels of their habitat. Our results elucidate the unique biology of this rodent, which elicits interest in the animal as a model for inflammatory research, although the findings require mechanistic corroborations.
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Lipopolisacáridos , Ratas Topo , Animales , Peso Corporal , Inflamación/inducido químicamente , Lipopolisacáridos/farmacología , Locomoción , Ratas Topo/fisiologíaRESUMEN
Naked mole-rats (NMR) and Damaraland mole-rats (DMR) exhibit extraordinary longevity for their body size, high tolerance to hypoxia and oxidative stress and high reproductive output; these collectively defy the concept that life-history traits should be negatively correlated. However, when life-history traits share similar underlying physiological mechanisms, these may be positively associated with each other. We propose that one such potential common mechanism might be the bioenergetic properties of mole-rats. Here, we aim to characterize the bioenergetic properties of two African mole-rats. We adopted a top-down perspective measuring the bioenergetic properties at the organismal, cellular, and molecular level in both species and the biological significance of these properties were compared with the same measures in Siberian hamsters and C57BL/6 mice, chosen for their similar body size to the mole-rat species. We found mole-rats shared several bioenergetic properties that differed from their comparison species, including low basal metabolic rates, a high dependence on glycolysis rather than on oxidative phosphorylation for ATP production, and low proton conductance across the mitochondrial inner membrane. These shared mole-rat features could be a result of evolutionary adaptation to tolerating variable oxygen atmospheres, in particular hypoxia, and may in turn be one of the molecular mechanisms underlying their extremely long lifespans.
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Mitocondrias , Ratas Topo , Animales , Hipoxia , Ratones , Ratones Endogámicos C57BL , Ratas Topo/fisiología , RespiraciónRESUMEN
Despite decades of research into the evolutionary drivers of sociality, we know relatively little about the underlying proximate mechanisms. Here we investigate the potential role of prolactin in the highly social naked mole-rat. Naked mole-rats live in large social groups but, only a small number of individuals reproduce. The remaining non-breeders are reproductively suppressed and contribute to burrow maintenance, foraging, and allo-parental care. Prolactin has well-documented links with reproductive timing and parental behaviour, and the discovery that non-breeding naked mole-rats have unusually high prolactin levels has led to the suggestion that prolactin may help maintain naked mole-rat sociality. To test this idea, we investigated whether urinary prolactin was correlated with cooperative behaviour and aggression. We then administered the prolactin-suppressing drug Cabergoline to eight female non-breeders for eight weeks and assessed the physiology and behaviour of the animals relative to controls. Contrary to the mammalian norm, and supporting previous findings for plasma, we found non-breeders had elevated urinary prolactin concentrations that were similar to breeding females. Further, prolactin levels were higher in heavier, socially dominant non-breeders. Urinary prolactin concentrations did not explain variation in working behaviour or patterns of aggression. Furthermore, females receiving Cabergoline did not show any behavioural or hormonal (progesterone) differences, and urinary prolactin did not appear to be suppressed in individuals receiving Cabergoline. While the results add to the relatively limited literature experimentally manipulating prolactin to investigate its role in reproduction and behaviour, they fail to explain why prolactin levels are high in non-breeding naked mole-rats, or how female non-breeding phenotypes are maintained.
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Ratas Topo , Prolactina , Animales , Cabergolina , Femenino , Ratas Topo/fisiología , Reproducción/fisiología , Conducta SocialRESUMEN
Sub-lethal effects, such as oxidative stress, can be linked to various breeding and thermophysiological strategies, which themselves can be linked to seasonal variability in abiotic factors. In this study, we investigated the subterranean, social living Natal mole-rat (Cryptomys hottentotus natalensis), which, unlike other social mole-rat species, implements heterothermy seasonally in an attempt to avoid exercise-induced hyperthermia and relies solely on behavioural reproductive suppression to maintain reproductive skew in colonies. Subsequently, we investigated how oxidative stress varied between season, sex and breeding status in Natal mole-rats. Oxidative markers included total oxidant status (TOS measure of total peroxides present), total antioxidant capacity (TAC), OSI (oxidative stress index) and malondialdehyde (MDA) to measure oxidative stress. Breeding and non-breeding mole-rats of both sexes were captured during the summer (wet season) and winter (dry season). Seasonal environmental variables (air temperature, soil temperature and soil moisture) had a significant effect on TOS, OSI and MDA, where season affected each sex differently. Unlike other social mole-rat species that use both physiological and behavioural means of reproductive suppression, no oxidative costs to reproduction were present in the Natal mole-rats. Males had significantly higher MDA than females, which was most apparent in summer (wet season). We conclude that the significant oxidative damage in males is a consequence of exercise-induced oxidative stress, exacerbated by increased burrow humidities and poorer heat dissipation abilities as a function of body mass. This study highlights the importance of both breeding and thermophysiological strategies in affecting oxidative stress.