Atypical behavioural, metabolic and thermoregulatory responses to hypoxia in the naked mole rat (Heterocephalus glaber)

Abstract

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.

The hypoxia tolerance of eight related African mole‐rat species rivals that of naked mole‐rats, despite divergent ventilatory and metabolic strategies in severe hypoxia

“…Previous work has shown that the NMR is among the most hypoxia‐tolerant mammals, responding to extreme hypoxia with no change in ventilation and large reductions in metabolism (Figure ). This is hypothesized to be the result of an evolutionary pressure exerted by low oxygen availability resulting from their fully fossorial and eusocial lifestyle, which could possibly be facilitated by a retention of neonatal traits .…”

“…One of the few fully fossorial species examined, the naked mole‐rat (NMR; Heterocephalus glaber ), is eusocial, and is among the most hypoxia‐tolerant mammals currently identified. NMRs are able to maintain consciousness and stay active even in severe hypoxia (<5% O 2 ), which are hallmarks of hypoxia tolerance . NMRs are able to withstand minutes of anoxia, hours of 3 kPa O 2 and days in 8 kPa O 2 , where hypoxia tolerance is partially mediated by depressions in metabolic rate, body temperature and behavioural activity with little change in ventilation, making them an exception with regard to the strategy by which semi‐fossorial and fully fossorial species tolerate hypoxia.…”

Naked mole rats activate neuroprotective proteins during hypoxia

“…Naked mole rats (NMRs) are remarkably long‐lived mammals and have evolved a suite of adaptations that have led to their cancer resistance, resistance to neurodegeneration, and survival of prolonged oxygen deprivation (Edrey et al, ; Liang, Mele, Wu, Buffenstein, & Hornsby, ; Pamenter, Lau, Richards, & Milsom, ; Park et al, ). Native to East Africa where they live in underground tunnel systems, NMRs are one of two eusocial mammalian species and studies have shown to fluctuate body temperature with ambient temperatures (Buffenstein & Yahav, ; Ilacqua, Kirby, & Pamenter, ; Kirby, Fairman, & Pamenter, ). It is possible that a combination of their heterothermic capacity, along with other molecular adaptations such as their enhanced hemoglobin oxygen binding (Johansen, Lykkeboe, Weber, & Maloiy, ) and their ability to switch to fructose‐driven metabolism allow them to endure periods of reduced oxygen availability (Park et al, ).…”

“…When oxygen is limited, the already low metabolic rates of NMRs are further depressed as they retreat into a hypometabolic state characterized by lowered heart rate, reduced mobility, alternate fuel usage, and lowered body temperature which itself would reinforce altered oxygen affinity and usage (Chung et al, ; Ilacqua et al, ; Kirby et al, ; Pamenter, Dzal, & Milsom, ; Pamenter, Dzal, Thompson, & Milsom, ). While it was originally believed that NMRs avoid oxidative damage as a part of their natural aging process, studies have since shown that NMRs accrue high levels of oxidative damage (Andziak & Buffenstein, ; Andziak et al, ; De Waal et al, ; Mitchell, Buffenstein, & Hulbert, ; Pérez et al, ).…”

Naked mole rat brain mitochondria electron transport system flux and H+ leak are reduced during acute hypoxia

“…NMRs exhibit a range of physiological adaptations that contribute to their hypoxia tolerance, including a high-affinity hemoglobin (Johansen et al, 1976), the ability to metabolize alternative glycolytic substrates in anoxia (Park et al, 2017), dramatic reductions in metabolic rate and ventilation (Pamenter et al, 2015) and body temperature and behaviour (Kirby et al, 2018;Houlahan et al, 2018;Ilacqua et al, 2017) in acute hypoxia, and metabolic remodelling in chronic hypoxia (Chung et al, 2016). Beyond systemic hypoxia tolerance, there is also evidence that NMR brain is tolerant of low O 2 and even ischemic stresses ex vivo.…”