Naked mole rats (NMRs) are among the most hypoxia-tolerant mammals. Other species respond to hypoxia by either escaping the hypoxic environment or drastically decreasing behavioural activity and body temperature () to conserve energy. However, NMRs rarely leave their underground burrows, which are putatively hypoxic and thermally stable near the NMRs' preferred Therefore, we asked whether NMRs are able to employ behavioural and thermoregulatory strategies in response to hypoxia despite their need to remain active and the minimal thermal scope in their burrows. We exposed NMRs to progressively deeper levels of hypoxia (from 21 to 0% O) while measuring their behaviour and Behavioural activity decreased 40-60% in hypoxia and decreased slightly in moderate hypoxia (5-9%) and then further with deeper hypoxia (3% O). However, even at 3% O NMRs remained somewhat active and warm, and continued to explore their environment. Remarkably, NMRs were active for greater than 90 s in acute anoxia and and metabolic rate decreased rapidly. We conclude that NMRs are adapted to remain awake and functional even at the extremes of their hypoxia-tolerance. This adaptation likely reflects variable and challenging levels of environmental hypoxia in the natural habitat of this species.

Hypoxia compromises aerobic energy production at the cellular level, but hypoxic environments are commonly encountered by mammals. In response, mammals typically exhibit compensatory physiological and behavioural adaptations that help to restore energetic homeostasis by reducing physical activity and body temperature (T b ) to lower metabolic demand. Naked mole rats (NMRs; Heterocephalus glaber) are among the most hypoxia-tolerant mammals identified but their behavioural and thermal responses to acute hypoxia are poorly characterized. Using behavioural tracking software, we examined the effects of acute hypoxia (1 h at 7% O 2 ) on physical activity and T b in animals held at their natural burrow temperature (30°C), or at temperatures above (38°C) or below (20°C). In separate experiments, we used respirometry to measure metabolic rate under the same conditions. Physical activity decreased~26-60% and T b decreased by~1.9-3.7°C during hypoxia in all temperatures. Normoxic metabolic rate was highest at 20°C, but was suppressed to similar rates in hypoxia across all temperatures. When animals were given the opportunity to escape their burrow temperature to either warmer or colder chambers during the hypoxic episode, NMRs surprisingly avoided the cold chamber, suggesting they are unable to take advantage of anapyrexia. Conversely, NMRs were able to use behavioural thermoregulation to maintain T b in hypoxia when given the choice of temperatures within and above their burrow temperature. Taken together, these findings indicate that NMRs respond to acute hypoxia with reversible decreases in physical activity, T b and metabolic rate across a range of ambient temperatures to reduce oxygen requirements.

Aims Burrowing mammals tend to be more hypoxia tolerant than non‐burrowing mammals and rely less on increases in ventilation and more on decreases in metabolic rate to tolerate hypoxia. Naked mole‐rats (Heterocephalus glaber, NMRs), eusocial mammals that live in large colonies, are among the most hypoxia‐tolerant mammals, and rely almost solely on decreases in metabolism with little change in ventilation during hypoxia. We hypothesized that the remarkable hypoxia tolerance of NMRs is an evolutionarily conserved trait derived from repeated exposure to severe hypoxia owing to their burrow environment and eusocial colony organization. Methods We used whole‐body plethysmography and indirect calorimetry to measure the hypoxic ventilatory and metabolic responses of eight mole‐rat species closely related to the NMR. Results We found that all eight species examined had a strong tolerance to hypoxia, with most species tolerating 3 kPa O2, Heliophobius emini tolerating 2 kPa O2 and Bathyergus suillus tolerating 5 kPa O2. All species examined employed a combination of increases in ventilation and decreases in metabolism in hypoxia, a response midway between that of the NMR and that of other fossorial species (larger ventilatory responses, lesser reductions in metabolism). We found that eusociality is not fundamental to the physiological response to hypoxia of NMRs as Fukomys damarensis, another eusocial species, was among this group. Conclusions Our data suggest that, while the NMR is unique in the pattern of their physiological response to hypoxia, eight closely related mole‐rat species share the ability to tolerate hypoxia like the current “hypoxia‐tolerant champion,” the NMR.

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Naked mole-rats are among the most hypoxia-tolerant mammals. During hypoxia, their body temperature (Tb) decreases via unknown mechanisms to conserve energy. In small mammals, non-shivering thermogenesis in brown adipose tissue (BAT) is critical to Tb regulation; therefore, we hypothesize that hypoxia decreases naked mole-rat BAT thermogenesis. To test this, we measure changes in Tb during normoxia and hypoxia (7% O2; 1–3 h). We report that interscapular thermogenesis is high in normoxia but ceases during hypoxia, and Tb decreases. Furthermore, in BAT from animals treated in hypoxia, UCP1 and mitochondrial complexes I-V protein expression rapidly decrease, while mitochondria undergo fission, and apoptosis and mitophagy are inhibited. Finally, UCP1 expression decreases in hypoxia in three other social African mole-rat species, but not a solitary species. These findings suggest that the ability to rapidly down-regulate thermogenesis to conserve oxygen in hypoxia may have evolved preferentially in social species.

Naked mole-rats are among the most hypoxia-tolerant mammals but have a poor thermoregulatory capacity due to their lack of insulating fur and fat, and small body size. In acute hypoxia, naked mole-rat body temperature (Tb) decreases to ambient temperature (Ta) but the mechanisms that underlie this thermoregulatory response are unknown. We hypothesized 1) that naked mole-rat blood vessels vasodilate during hypoxia to shunt heat toward the body surface and/or 2) that they augment heat loss through evaporative cooling. Using open-flow respirometry (indirect calorimetry) we explored metabolic and thermoregulatory strategies of naked mole-rats exposed to hypoxia (7% O2 for 1 hr) at two relative humidities (RH; 50 or 100% water saturation), and in two Ta's (25 and 30°C), alone, and following treatment with the vasoconstrictor angiotensin II (ANGII). We found that Tb and metabolic rate decreased in hypoxia across all treatment groups but that neither RH nor ANGII effected either variable in hypoxia. Conversely, both Tb and metabolic rate were reduced in 100% RH or by ANGII treatment in normoxia at 25°C, and therefore the absolute change in both variables with the onset of hypoxia was reduced when vasodilation or evaporative cooling were prevented. We conclude that naked mole-rats employ evaporative cooling and vasodilation to thermoregulate in normoxia and in 25°C but that neither mechanism is involved in thermoregulatory changes during acute hypoxia. These findings suggest that NMRs may employ passive strategies such as reducing thermogenesis to reduce Tb in hypoxia, which would support metabolic rate suppression.

A minimalist fluorogenic probe is presented capable of the mapping of aldehydic load through live cell microscopy.

A new CEST-MRI contrast agent, 2-HYNIC, capable of sensing aromatic aldehydes is reported. Pyridoxal 5’-phosphate, a key Vitamin B6 metabolite necessary for > 140 biotransformations was mapped by CEST-MRI in...