scholarly journals Life-long exposure to hypoxia affects metabolism and respiratory physiology across life stages in high-altitude deer mice (Peromyscus maniculatus)

2020 ◽  
Vol 224 (1) ◽  
pp. jeb237024 ◽  
Author(s):  
Catherine M. Ivy ◽  
Graham R. Scott
Keyword(s):  
High Altitude ◽  
Peromyscus Maniculatus ◽  
Adult Life ◽  
Respiratory Physiology ◽  
Deer Mice ◽  
Continuous Exposure ◽  
Life Stages ◽  
Hypoxia Exposure ◽  
In Captivity ◽  
Haemoglobin Content

ABSTRACTHypoxia exposure can have distinct physiological effects between early developmental and adult life stages, but it is unclear how the effects of hypoxia may progress during continuous exposure throughout life. We examined this issue in deer mice (Peromyscus maniculatus) from a population native to high altitude. Mice were bred in captivity in one of three treatment groups: normoxia (controls), life-long hypoxia (∼12 kPa O2 from conception to adulthood) and parental hypoxia (normoxia from conception to adulthood, but parents previously exposed to hypoxia). Metabolic, thermoregulatory and ventilatory responses to progressive stepwise hypoxia and haematology were then measured at post-natal day (P) 14 and 30 and/or in adulthood. Life-long hypoxia had consistent effects across ages on metabolism, attenuating the declines in O2 consumption rate (V̇O2) and body temperature during progressive hypoxia compared with control mice. However, life-long hypoxia had age-specific effects on breathing, blunting the hypoxia-induced increases in air convection requirement (quotient of total ventilation and V̇O2) at P14 and P30 only, but then shifting breathing pattern towards deeper and/or less frequent breaths at P30 and adulthood. Hypoxia exposure also increased blood–O2 affinity at P14 and P30, in association with an increase in arterial O2 saturation in hypoxia at P30. In contrast, parental hypoxia had no effects on metabolism or breathing, but it increased blood–O2 affinity and decreased red cell haemoglobin content at P14 (but not P30). Therefore, hypoxia exposure has some consistent effects across early life and adulthood, and some other effects that are unique to specific life stages.

scholarly journals Distinct Mechanisms Underlie Developmental Plasticity and Adult Acclimation of Thermogenic Capacity in High-Altitude Deer Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Catherine M. Ivy ◽  
Haley Prest ◽  
Claire M. West ◽  
Graham R. Scott
Keyword(s):  
High Altitude ◽  
Developmental Plasticity ◽  
Adult Life ◽  
Lung Ventilation ◽  
Deer Mice ◽  
Life Stages ◽  
Physiological Plasticity ◽  
Physiological Mechanisms ◽  
In Captivity ◽  
The Relationship

Developmental plasticity can elicit phenotypic adjustments that help organisms cope with environmental change, but the relationship between developmental plasticity and plasticity in adult life (e.g., acclimation) remains unresolved. We sought to examine developmental plasticity and adult acclimation in response to hypoxia of aerobic capacity (V̇O2max) for thermogenesis in deer mice (Peromyscus maniculatus) native to high altitude. Deer mice were bred in captivity and exposed to normoxia or one of four hypoxia treatments (12 kPa O2) across life stages: adult hypoxia (6–8 weeks), post-natal hypoxia (birth to adulthood), life-long hypoxia (before conception to adulthood), and parental hypoxia (mice conceived and raised in normoxia, but parents previously exposed to hypoxia). Hypoxia during perinatal development increased V̇O2max by a much greater magnitude than adult hypoxia. The amplified effect of developmental hypoxia resulted from physiological plasticity that did not occur with adult hypoxia – namely, increases in lung ventilation and volume. Evolved characteristics of deer mice enabled developmental plasticity, because white-footed mice (P. leucopus; a congener restricted to low altitudes) could not raise pups in hypoxia. Parental hypoxia had no persistent effects on V̇O2max. Therefore, developmental plasticity can have much stronger phenotypic effects and can manifest from distinct physiological mechanisms from adult acclimation.

scholarly journals Genetic variation in haemoglobin alters breathing in high-altitude deer mice

2021 ◽  
Author(s):  
Catherine M. Ivy ◽  
Oliver H. Wearing ◽  
Chandrasekhar Natarajan ◽  
Rena M. Schweizer ◽  
Natalia Gutiérrez-Pinto ◽  
...  
Keyword(s):  
Genetic Variation ◽  
High Altitude ◽  
Globin Gene ◽  
Respiratory Physiology ◽  
Deer Mice ◽  
Emergent Properties ◽  
Mixed Genetic Background ◽  
Hypoxia Adaptation ◽  
Globin Gene Expression

ABSTRACTPhysiological systems often have emergent properties but the effects of genetic variation on physiology are often unknown, which presents a major challenge to understanding the mechanisms of phenotypic evolution. We investigated the in vivo effects on respiratory physiology of genetic variants in haemoglobin (Hb) that contribute to hypoxia adaptation in high-altitude deer mice (Peromyscus maniculatus). We created F2 inter-population hybrids of highland and lowland deer mice to test the phenotypic effects of α- and β-globin variants on a mixed genetic background. High-altitude genotypes were associated with breathing phenotypes that enhance O2 uptake in hypoxia, including a deeper more effective breathing pattern and an augmented hypoxic ventilatory response. These effects could not be explained by erythrocyte Hb-O2 affinity or globin gene expression in the brainstem. Therefore, adaptive variation in haemoglobin can have unexpected effects on physiology that are distinct from the canonical function of this protein in circulatory O2 transport.

scholarly journals Development of homeothermic endothermy is delayed in high-altitude native deer mice ( Peromyscus maniculatus)

2019 ◽  
Vol 286 (1907) ◽  
pp. 20190841 ◽  
Author(s):  
Cayleih E. Robertson ◽  
Glenn J. Tattersall ◽  
Grant B. McClelland
Keyword(s):  
High Altitude ◽  
Peromyscus Maniculatus ◽  
Common Garden ◽  
Deer Mice ◽  
Ambient Temperatures ◽  
Equivalent Age ◽  
Brown Adipose ◽  
Challenging Environment ◽  
Sympathetic Regulation ◽  
Saving Measure

Altricial mammals begin to independently thermoregulate during the first few weeks of postnatal development. In wild rodent populations, this is also a time of high mortality (50–95%), making the physiological systems that mature during this period potential targets for selection. High altitude (HA) is a particularly challenging environment for small endotherms owing to unremitting low O 2 and ambient temperatures. While superior thermogenic capacities have been demonstrated in adults of some HA species, it is unclear if selection has occurred to survive these unique challenges early in development. We used deer mice ( Peromyscus maniculatus ) native to high and low altitude (LA), and a strictly LA species ( Peromyscus leucopus ), raised under common garden conditions, to determine if postnatal onset of endothermy and maturation of brown adipose tissue (BAT) is affected by altitude ancestry. We found that the onset of endothermy corresponds with the maturation and activation of BAT at an equivalent age in LA natives, with 10-day-old pups able to thermoregulate in response to acute cold in both species. However, the onset of endothermy in HA pups was substantially delayed (by approx. 2 days), possibly driven by delayed sympathetic regulation of BAT. We suggest that this delay may be part of an evolved cost-saving measure to allow pups to maintain growth rates under the O 2 -limited conditions at HA.

scholarly journals Evolved changes in breathing and CO2 sensitivity in deer mice native to high altitudes

2018 ◽  
Vol 315 (5) ◽  
pp. R1027-R1037 ◽  
Author(s):  
Catherine M. Ivy ◽  
Graham R. Scott
Keyword(s):  
High Altitude ◽  
Breathing Pattern ◽  
Ventilatory Response ◽  
Deer Mice ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Responses ◽  
In Captivity ◽  
Generation Progeny ◽  
First And Second Generation ◽  
Hypoxia Acclimation

We examined the control of breathing by O2 and CO2 in deer mice native to high altitude to help uncover the physiological specializations used to cope with hypoxia in high-altitude environments. Highland deer mice ( Peromyscus maniculatus) and lowland white-footed mice ( P. leucopus) were bred in captivity at sea level. The first and second generation progeny of each population was raised to adulthood and then acclimated to normoxia or hypobaric hypoxia (12 kPa O2, simulating hypoxia at ~4,300 m) for 6–8 wk. Ventilatory responses to poikilocapnic hypoxia (stepwise reductions in inspired O2) and hypercapnia (stepwise increases in inspired CO2) were then compared between groups. Both generations of lowlanders appeared to exhibit ventilatory acclimatization to hypoxia (VAH), in which hypoxia acclimation enhanced the hypoxic ventilatory response and/or made the breathing pattern more effective (higher tidal volumes and lower breathing frequencies at a given total ventilation). In contrast, hypoxia acclimation had no effect on breathing in either generation of highlanders, and breathing was generally similar to hypoxia-acclimated lowlanders. Therefore, attenuation of VAH may be an evolved feature of highlanders that persists for multiple generations in captivity. Hypoxia acclimation increased CO2 sensitivity of breathing, but in this case, the effect of hypoxia acclimation was similar in highlanders and lowlanders. Our results suggest that highland deer mice have evolved high rates of alveolar ventilation that are unaltered by exposure to chronic hypoxia, but they have preserved ventilatory sensitivity to CO2.

scholarly journals Acclimatization of low altitude-bred deer mice (Peromyscus maniculatus) to high altitude

2018 ◽  
Vol 125 (5) ◽  
pp. 1411-1423 ◽  
Author(s):  
D. Merrill Dane ◽  
Khoa Cao ◽  
Hua Lu ◽  
Cuneyt Yilmaz ◽  
Jamie Dolan ◽  
...  
Keyword(s):  
Blood Flow ◽  
High Altitude ◽  
Lung Volume ◽  
Pulmonary Blood Flow ◽  
Peromyscus Maniculatus ◽  
Deer Mice ◽  
Alveolar Type ◽  
Type I ◽  
Lower Altitude ◽  
Lung Expansion

A colony of deer mice subspecies ( Peromyscus maniculatus sonoriensis) native to high altitude (HA) has been maintained at sea level for 18–20 generations and remains genetically unchanged. To determine if these animals retain responsiveness to hypoxia, one group (9–11 wk old) was acclimated to HA (3,800 m) for 8 wk. Age-matched control animals were acclimated to a lower altitude (LA; 252 m). Maximal O2 uptake (V̇o2max) was measured at the respective altitudes. On a separate day, lung volume, diffusing capacity for carbon monoxide (DLCO), and pulmonary blood flow were measured under anesthesia using a rebreathing technique at two inspired O2 tensions. The HA-acclimated deer mice maintained a normal V̇o2max relative to LA baseline. Compared with LA control mice, antemortem lung volume was larger in HA mice in a manner dependent on alveolar O2 tension. Systemic hematocrit, pulmonary blood flow, and standardized DLCO did not differ significantly between groups. HA mice showed a higher postmortem alveolar-capillary hematocrit, larger alveolar ducts, and smaller distal conducting structures. In HA mice, absolute volumes of alveolar type I epithelia and endothelia were higher whereas that of interstitia was lower than in LA mice. These structural changes occurred without a net increase in whole-lung septal tissue-capillary volumes or surface areas. Thus, deer mice bred and raised to adulthood at LA retain phenotypic plasticity and adapt to HA without a decrement in V̇o2max via structural (enlarged airspaces, alveolar septal remodeling) and nonstructural (lung expansion under hypoxia) mechanisms and without an increase in systemic hematocrit or compensatory lung growth. NEW & NOTEWORTHY Deer mice ( Peromyscus maniculatus) are robust and very active mammals that are found across the North American continent. They are also highly adaptable to extreme environments. When introduced to high altitude they retain remarkable adaptive ability to the low-oxygen environment via lung expansion and remodeling of existing lung structure, thereby maintaining normal aerobic capacity without generating more red blood cells or additional lung tissue.

scholarly journals Ontogenesis of evolved changes in respiratory physiology in deer mice native to high altitude

2020 ◽  
Vol 223 (5) ◽  
pp. jeb219360 ◽  
Author(s):  
Catherine M. Ivy ◽  
Mary A. Greaves ◽  
Elizabeth D. Sangster ◽  
Cayleih E. Robertson ◽  
Chandrasekhar Natarajan ◽  
...  
Keyword(s):  
High Altitude ◽  
Respiratory Physiology ◽  
Deer Mice

scholarly journals Coordinated changes across the O 2 transport pathway underlie adaptive increases in thermogenic capacity in high-altitude deer mice

2020 ◽  
Vol 287 (1927) ◽  
pp. 20192750 ◽  
Author(s):  
Kevin B. Tate ◽  
Oliver H. Wearing ◽  
Catherine M. Ivy ◽  
Zachary A. Cheviron ◽  
Jay F. Storz ◽  
...  
Keyword(s):  
High Altitude ◽  
Complex Traits ◽  
Deer Mice ◽  
Transport Pathway ◽  
Physiological Mechanisms ◽  
Critical Determinant ◽  
In Captivity ◽  
Low Altitude ◽  
Hypoxia Acclimation ◽  
Thermogenic Capacity

Animals native to the hypoxic and cold environment at high altitude provide an excellent opportunity to elucidate the integrative mechanisms underlying the adaptive evolution and plasticity of complex traits. The capacity for aerobic thermogenesis can be a critical determinant of survival for small mammals at high altitude, but the physiological mechanisms underlying the evolution of this performance trait remain unresolved. We examined this issue by comparing high-altitude deer mice ( Peromyscus maniculatus ) with low-altitude deer mice and white-footed mice ( P. leucopus ). Mice were bred in captivity and adults were acclimated to each of four treatments: warm (25°C) normoxia, warm hypoxia (12 kPa O 2 ), cold (5°C) normoxia or cold hypoxia. Acclimation to hypoxia and/or cold increased thermogenic capacity in deer mice, but hypoxia acclimation led to much greater increases in thermogenic capacity in highlanders than in lowlanders. The high thermogenic capacity of highlanders was associated with increases in pulmonary O 2 extraction, arterial O 2 saturation, cardiac output and arterial–venous O 2 difference. Mechanisms underlying the evolution of enhanced thermogenic capacity in highlanders were partially distinct from those underlying the ancestral acclimation responses of lowlanders. Environmental adaptation has thus enhanced phenotypic plasticity and expanded the physiological toolkit for coping with the challenges at high altitude.

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