High Altitude Stress Research Articles

Convergent evolution of SOCS4 between yak and Tibetan antelope in response to high-altitude stress

Convergence often occurs when organisms with different ancestors adopt similar adaptations to environmental stresses. Convergent (sometimes called parallel) evolution at the genetic level is now known to be more common than previously suspected. Studying convergent evolution at the molecular level makes it possible to gain a better understanding of the common mechanisms deployed by different species. Yak (Bos grunniens) and Tibetan antelope (Pantholops hodgsonii), which are endemic to the Qinghai–Tibetan Plateau, both have numerous traits that are adaptive to high altitudes. However, it is still unclear whether these two species have undergone adaptive convergence at the genetic level. We used genomic data to detect possible examples of convergent evolution between yak and Tibetan antelope. We found that one gene, SOCS4, which is involved in the regulation of HIF-1α, showed a signature of convergent evolution. Our results have provided clues that may be important for understanding high-altitude adaptations in animals.

A pharmacological investigation of Hippophae salicifolia (HS) and Hippophae rhamnoides turkestanica (HRT) against multiple stress (C-H-R): an experimental study using rat model.

Hippophae salicifolia (HS) and Hippophae rhamnoides turkestanica (HRT) are abundantly found species of Hippophae in Himalayan region of India. As these plants thrive under extreme climatic conditions, it is suspected that these plants must have a unique adaptogenic property against high-altitude stress. To keeping these views in our mind, the present study was planned to evaluate the mechanism of action of aqueous extract of HS and aqueous extract of HRT against multiple stress [cold-hypoxia-restraint (C-H-R)] for their adaptogenic activity. The present study reported the adaptogenic activity of HS in facilitating tolerance to multiple stress, CHR in rats. Pre-treatment with aqueous extract of HS significantly attenuated reactive oxygen species (ROS) production, protein oxidation, and lipid peroxidation and also showed role in maintaining antioxidant status as similar to control rats. Since protein oxidation was decreased by pre-treatment of HS, protein homeostasis was also sustained by regulation of heat shock proteins (HSP70 and HSP60). Interestingly, heme oxygenase-1 (HO-1), Vascular Endothelial Growth Factor (VEGF), and nitric oxide (NO) level was also increased in HS pre-treated rats depicted its adaptogenic activity against multiple stress, CHR. Conclusively, aqueous extract of HS could use an adaptogen for high altitude-associated multiple stress (CHR).

Transcriptomic analysis provides insight into high-altitude acclimation in domestic goats

Domestic goats are distributed in a wide range of habitats and have acclimated to their local environmental conditions. To investigate the gene expression changes of goats that are induced by high altitude stress, we performed RNA-seq on 27 samples from the three hypoxia-sensitive tissues (heart, lung, and skeletal muscle) in three indigenous populations from distinct altitudes (600m, 2000m, and 3000m). We generated 129Gb of high-quality sequencing data (~4Gb per sample) and catalogued the expression profiles of 12,421 annotated hircine genes in each sample. The analysis showed global similarities and differences of high-altitude transcriptomes among populations and tissues as well as revealed that the heart underwent the most high-altitude induced expression changes. We identified numerous differentially expressed genes that exhibited distinct expression patterns, and nonsynonymous single nucleotide variant-containing genes that were highly differentiated between the high- and low-altitude populations. These genes have known or potential roles in hypoxia response and were enriched in functional gene categories potentially responsible for high-altitude stress. Therefore, they are appealing candidates for further investigation of the gene expression and associated regulatory mechanisms related to high-altitude acclimation.

Freshwater algal diversity of the South-Tajik Depression in a high-mountainous extreme environment, Tajikistan

The research on algal communities' response to altitude and altitude-related climatic conditions is sparse. So far, a full, accessible list of algae from the water bodies of the South-Tajik Depression has not been available. We compiled an algal species list of 1190 taxa that were revealed by us or listed in references in the South-Tajik Depression high-mountain rivers Kafirnigan, Vakhsh, Kyzylsu, Yakhsu, and Tairsu and in the lakes of its basin. The altitude gradient of the studied area is about 2500 m above sea level. An altitude-related algal diversity analysis was done with help of statistics and bioindication. The Willis curve for the distribution of species to genera had a trend line of R 2 = 0.92. A multivariate analysis was used for quantitative estimates of the ecological tolerance ranges of critical species and for detecting cardinal factors and trends at local water bodies to global levels of biodiversity evolution. Our analysis shows that species distribution was strongly affected by altitude and altitude-related climatic variables. Statistical methods revealed that temperatures stimulate algal species diversity, while precipitation and altitude suppress it. One of the floristic complexity criteria is the average species richness of the algal genera or the infraspecies to species ratio, which increased from 1.12 to 1.20 and reflects increases in structural complexity with altitude. Therefore, high altitude stresses algal communities and stimulates species polymorphism as a compensatory mechanism for algal species survival. Our approach is pertinent to the problem of floristic differentiation under climate change and climatic instability.

Biochemical Aspects of Acclimatization of Man to High Altitude Stress

The paper reviews the biochemical aspects of acclimatization of human body to high altitude with particular reference to the adaptive changes in Skeletal muscles, hepatic function, adrenal function and carbohydrate metabolism.

Evidence of adaptive evolution of alpine pheasants to high-altitude environment from mitogenomic perspective

Adaptive evolutions to high-altitude adaptation have been intensively studied in mammals. However, considering the additional vertebrate groups, new perception regarding selection challenged by high-altitude stress on mitochondrial genome can be gained. To test this hypothesis, we compiled and analyzed the mitochondrial genomes of 5 alpine pheasants and 12 low-altitude species in Phasianidae. The results that evolutionary rates of ATP6 and ND6 showing significant fluctuation among branches when involved with five alpine pheasants revealed both genes might have implications with adapting to highland environment. The radical physico-chemical property changes identified by the modified MM01 model, including composition (C) and equilibrium constant (ionization of COOH) (Pk′) in ATP6 and beta-structure tendencies (Pβ), Pk′, and long-range non-bonded energy (El) in ND6, suggested that minor overall adjustments in size, protein conformation and relative orientation of reaction interfaces have been optimized to provide the ideal environments for electron transfer, proton translocation and generation of adenosine triphosphate (ATP). Additionally, three unique substitution sites were identified under selection in ND6, which could be potentially important adaptive changes contributing to cellular energy production. Our findings suggested that adaptive evolution may occur in alpine pheasants, which are an important complement to the knowledge of genetic mechanisms against the high-altitude environment in non-mammal animals.

Importance of Functional Ingredients in Yak Milk-Derived Food on Health of Tibetan Nomads Living Under High-Altitude Stress: A Review

Tibetan nomads have lived since ancient times in the unique and harsh environment of the Qinghai-Tibetan Plateau with average altitudes over 4000 m. These people have been able to live and multiply healthily over numerous generations under the extreme stress of high-altitude environment, including cold, hypoxia, and strong ultraviolet radiation, and with a simple diet devoid of vegetables and fruits for most of the year. Their survival depends heavily on yak milk, and its products comprise the main portion of their daily diet. In this review, yak milk and its derived products are examined in detail and compared with milk from other ruminant species. Yak milk products seem to be particularly rich in functional and bioactive components, which may play a role in maintaining the health status of Tibetan nomads. This includes particular profiles of amino acids and fatty acids, and high levels of antioxidant vitamins, specific enzymes, and bacteria with probiotic activity (yoghurt is the main food). Based on that, it is proposed that the Tibetan nomads have developed a nutritional mechanism adapted to cope with the specific challenges posed by the environment of the world's highest plateau. Systematic studies are required to demonstrate this in a more mechanistic way.

Myocardial ER chaperone activation and protein degradation occurs due to synergistic, not individual, cold and hypoxic stress

Environmental stress at high altitude affects the myocardium at the physiological and molecular level. Characterized by hypobaric hypoxia and low temperatures, the cumulative impact of these stressors on the protein folding homeostasis in the heart is yet unexplored. The present study evaluates the collective effect of cold and hypoxia on the myocardial protein oxidation and activation of the endoplasmic reticulum (ER) stress response. Adult rats were exposed to either a singular acute stress of cold (10 °C; C), hypobaric hypoxia (7620 m; H) or simultaneously to both cold and hypobaric hypoxia (CH) for 6 h. Hypoxic stress amplified the free radical generation in H and CH groups, leading to enhanced HIF-1α expression. Coupled to cold stress, reduced oxygen availability caused substantial protein oxidative modifications, as well as cardiac tissue injury and matrix remodeling, evident in the histological staining. Presence of oxidized proteins caused a significant upregulation in expression of ER chaperones GRP78 and PDI in the cold hypoxia exposed animals. Enhanced proteolytic activity signaled the removal of misfolded proteins. Linked intricately to cellular stress response, cell survival kinases were expressed higher in CH group; however apoptotic CHOP (C/EBP homologous protein) expression remained unaltered. Administration of ER stress inducer, tunicamycin along with cold hypoxic stress, caused a discernible increase in protein oxidation and GRP78 expression, along with a significant elevation in proteasome and apoptotic activity. Highlighting the significance of a synergistic, rather than individual, effect of low oxygen and temperature on the protein folding machinery, our study provides evidence for the activation of ER stress response in the myocardium under acute high altitude stress.

A Study of High-Altitude Hypoxia-Induced Cell Stress in Murine Model

We evaluated the effects of high-altitude hypoxic stress in the murine model. For this purpose, 36 CR-mice in group A were maintained at the altitude of 3,820 m for hypoxia-induced factor (HIF)-1α expression analysis by immunohistochemistry. The 36 Wistar rats in group B were maintained in low-pressure (400-420 kPa) oxygen chamber, and the effects of hypoxia on myocardial mitochondria were studied. In the 36 CR-mice of group C, plasma vascular endothelial growth factor (VEGF) levels were determined using strept-avidin-biotin complex/diaminobenzidine method after exposure to different altitudes/O(2)-concentrations. The data show that in experimental group A1, endothelin (ET)-1α concentrations gradually increased whereas HIF-1α expression in myocardial cells was higher (P < 0.01) than in control group A2. In rats of group B, the myocardial mitochondria numbers were reduced during the initial phase of acute stress response to hypoxia and cellular injury but, later, mitochondrial numbers were restored to normal values. In mice of experimental group C1, plasma VEGF concentrations increased under hypoxia, which were significantly higher (P < 0.01) than those of control group C2. We, therefore, concluded that high-altitude hypoxia: (i) induced HIF-1α expression; (ii) prompted adaptation/acclimatization after initial stress and cellular injury; and (iii) enhanced VEGF expression in murine.

Genomic insights into adaptation to high-altitude environments.

Elucidating the molecular genetic basis of adaptive traits is a central goal of evolutionary genetics. The cold, hypoxic conditions of high-altitude habitats impose severe metabolic demands on endothermic vertebrates, and understanding how high-altitude endotherms cope with the combined effects of hypoxia and cold can provide important insights into the process of adaptive evolution. The physiological responses to high-altitude stress have been the subject of over a century of research, and recent advances in genomic technologies have opened up exciting opportunities to explore the molecular genetic basis of adaptive physiological traits. Here, we review recent literature on the use of genomic approaches to study adaptation to high-altitude hypoxia in terrestrial vertebrates, and explore opportunities provided by newly developed technologies to address unanswered questions in high-altitude adaptation at a genomic scale.

Plasma proANP 1-98 Response During High Altitude Stress: Effect of Age and Ethnicity

Acclimatization to high altitude (HA) is accompanied by decrease in plasma atrial natriuretic peptide (ANP). On the other hand, circulating levels of the hormone are known to be influenced by age and ethnicity. The impact of these factors on ANP response during prolonged HA exposure remains unexplored. Hence, this study was conducted to examine possible age and ethnic variation in plasma proANP(1-98) levels in men after 3 to 4 weeks at HA. Lowlanders (LL) were studied at sea level (SL) and after 3 to 4 weeks at an altitude of approximately 4500 m. The LL group comprised Rajput (n = 48), Gorkha (n = 40), and South Indian (n = 43) ethnicities. Another group of HA natives (Ladakhi, n = 40) were studied at approximately 4500 m only. Subjects were between 20 and 50 years of age. Estimation of plasma proANP(1-98) and biochemical, hematologic, and physiologic evaluation was done. In LL at HA, proANP(1-98) levels decreased (P < .001); plasma arginine vasopressin decreased (P < .05 in Rajputs and South Indians); and total protein, hemoglobin, and hematocrit increased (P < .05). Heart rate increased (P < .05), whereas arterial oxygen saturation decreased (P < .05) in all LL at HA. Ethnicity but not age variation in proANP(1-98) was observed under HA stress. In HA natives, plasma proANP(1-98) was higher than LL at HA and did not exhibit any age variation. Plasma proANP(1-98) levels, reflecting medium-term ANP secretion, decrease during prolonged exposure to HA in LL. This is due to diuresis leading to plasma volume reduction that occurs during the acclimatization process. Ethnicity but not age variation is associated with plasma proANP(1-98) under HA stress.

Liver Transplantation in a Patient with Pulmonary Hypertension at High Altitude

Chronic hypoxia at high altitude stresses many of the body's homeostatic mechanisms. As a consequence, the body develops alveolar hypoxia, hypoxemia, and polycythemia, which in turn causes vasoconstriction, pulmonary hypertension, and an increased risk of atherothrombotic complications. We report a successful liver transplantation in a patient with pulmonary hypertension who lives 4500 m above sea level. Pulmonary hypertension and hypercoagulable state induced by chronic hypoxia at high altitude may increase the risk of cardiopulmonary complication and perioperative mortality. The patient was discharged in good condition with normal liver function at the 34th postoperative day. After 41 months of follow-up, the patient is alive and well with a continued normalization of hepatic function and is continuing to live at 4500 m above sea level.

Splenic Syndrome: A Rare Indication for Splenectomy

Splenic infarction due to sickle cell trait and high-altitude stress has been reported in the literature. Contributing factors leading to infarction are degree of altitude stress and status of physical condition. Medical therapy, which consists of evacuation from high altitude, intravenous fluids, supplemental oxygen, and pain control, has been the mainstay of treatment. However, some patients require surgical intervention. We describe six patients with sickle cell trait who sustained splenic infarctions due to high-altitude stress; two of these patients required splenectomy for near-total splenic necrosis and intractable pain. A review of the literature demonstrates that the common indications for splenectomy are splenic rupture, extensive splenic necrosis, or persistent abdominal pain.

Glutathione Metabolism Under High-Altitude Stress and Effect of Antioxidant Supplementation

Humans have a number of mechanisms for protection against reactive oxygen species, but under stressful conditions these defenses are not completely successful. Glutathione plays an important role in protection against free radicals and reactive oxygen species induced damages. The present study was undertaken to understand the effect of high-altitude (HA) exposure on glutathione metabolism and antioxidant status along with the effects of N-acetyl cysteine (NAC) and vitamin E supplementation in humans. The study was conducted on 30 healthy male volunteers (age 22.9 +/- 2.6, mean +/- SD) divided into three groups. Group 1 was placebo control and 2 and 3 were supplemented with 400 mg of NAC or vitamin E, respectively, per day. The study was conducted initially at sea level (Phase I, 320 m); then the subjects were taken to high altitude (Phase II, 3600 m) by air. After a week at this altitude, subjects ascended on foot to an altitude of 4580 m (Phase III). Significant decreases in reduced glutathione and increases in oxidized glutathione levels were observed on HA exposure. Increase in glutathione peroxidase and glutathione reductase levels were also observed on HA exposure. Lower levels of plasma vitamin C and total antioxidant status were observed during HA exposure. The changes observed were less in the supplemented groups as compared to placebo control. Results indicate that HA exposure adversely affects glutathione metabolism and antioxidant defense mechanisms and these changes can be ameliorated through supplementation of NAC and vitamin E.

Twentieth-century Scots Pine Growth Variations in the Central Scandinavian Mountains Related to Climate Change

Climate-sensitive trees are valuable for reconstructing past climates, but they also can be used to assess the impacts of environmental change, such as global warming, on forest ecosystems. Growth variability and growth responses to climate of a Scots pine (Pinus sylvestris L.) tree-ring width chronology, from the treeline in the central Scandinavian Mountains, were studied throughout the 20th century. Summer temperatures, especially in July, were the most influential climate factor for tree growth. Correlation analyses in three 30-yr periods showed that growth responses to climate varied through time, being particularly low in 1931 to 1960. Nevertheless, tree growth around 1950 was the highest for 320 yr, implying optimal growth conditions. This growth increase appears to be a response to increased summer temperatures, a lengthening of the growing season, and a temporal change in the atmospheric circulation pattern. Despite a continuation of seemingly favorable growth conditions in the latter half of the 20th century, pine growth decreased after the 1950s. It appears that high-altitude pine experienced stress that surpassed the positive effect of improved growth season climate. Since pine growth decline coincided with an unprecedented strong and positive period of wintertime North Atlantic Oscillation (NAO), a measure of strength of westerly winds bringing mild and moist air masses over Scandinavia, it is proposed that milder and wetter winters caused growth stress, and hence reduced growth, in high-altitude central Sweden.

Biochemical and immunological changes on oral glutamate feeding in male albino rats

High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32 +/- 2 degrees C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress.

Hypobaric hypoxia and hedonic matrix in rats.

This study was carried out to evaluate the effect of continuous exposure to hypobaric hypoxia on the feeding behavior and taste responses of rats, under simulated conditions of a high altitude (HA) of 7,620 m for 21 h a day and consecutively for 18 d, which more closely resembles actual field conditions. Their food, water intake and body weight were recorded daily, and blood sugar was estimated once a week. All the parameters were recorded for a period of 18 d each, before, during, and after exposure to simulated HA. The results show a decrease in daily food and water intake and body weight, and mild hypoglycemia during hypoxic exposure. Single-bottle and two-bottle tests showed a preference for sweet solutions over water, citric acid, sodium chloride, and quinine sulfate during exposure. The two-bottle test showed a preference for glucose over calorically-inert saccharine. The continuous exposure in this study produced qualitatively similar but quantitatively accentuated results as compared to intermittent 6 h exposure contiguously for 21 d. High-altitude stress appears to influence food intake such that sensory cues assume greater significance during feeding behavior.

Effect of high-altitude hypoxia on feeding responses and hedonic matrix in rats.

Albino male rats (n = 78) were exposed to a simulated high altitude (HA) equivalent to 7,620 m for 6 h daily, contiguously for a period of 21 days, to study their feeding behavior and gustatory responses. Their food, water intake, and body weight were recorded daily, and blood sugar and blood insulin were estimated once a week. All the parameters were recorded for a period of 3 wk each before, during, and after exposure to simulated HA. The results show a decrease in daily food and water intakes and body weight and mild hyperglycemia and hyperinsulinemia during hypoxic exposure. The 1-h single-bottle taste solution test showed a preference for sweet solutions (13% glucose and 0.2% saccharine) over citric acid (0.16%), sodium chloride (0.9%), and quinine sulfate (0.001%) during exposure to simulated HA. The 1-h two-bottle test containing glucose (calories plus taste) and saccharine (taste but no calories) administration showed a preference for the glucose solution over the saccharine solution. The trend of the 1-h intake of all test solutions also showed a reversal to preexposure levels after termination of HA hypoxia. It would appear that high-altitude stress influences food intake in a manner that sensory cues (e.g., preference for sweet substances) become more important.

Overview of spaceflight immunology studies.

The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.

Effect of high-altitude ecological and experimental stresses on the platelet-vascular wall system

Effect of high-altitude ecological and experimental stresses on the platelet-vascular wall system