Chronic Hypobaric Hypoxia Exposure Research Articles

Insight into the role of myokines and myogenic regulatory factors under hypobaric hypoxia induced skeletal muscle loss

ABSTRACT Background The present study aimed to analyse the role of myokines and the regeneration capacity of skeletal muscle during chronic hypobaric hypoxia (CHH). Methods Male Sprague-Dawley rats were exposed to hypobaric hypoxia (HH) for 1d, 3d and 7d. Results Exposure to HH enhanced the levels of decorin, irisin, IL-6 and IL-15 till 3 days of hypoxia and on 7 day of exposure, no significant changes were observed in relation to control. A significant upregulation in myostatin, activated protein kinase, SMAD3, SMAD4, FOXO-1, MURF-1 expression was observed with prolonged HH exposure as compared to normoxic control. Further, myogenesis-related markers, PAX-7, Cyclin D1 and myogenin were downregulated during CHH exposure in comparison to control. Energy metabolism regulators such as Sirtuin 1, proliferator-activated receptor gamma coactivator-1α and GLUT-4, were also increased on 1-d HH exposure that showed a declining trend on CHH exposure. Conclusions These results indicated the impairment in the levels of myokines and myogenesis during prolonged hypoxia. CHH exposure enhanced the levels of myostatin and reduced the regeneration or repair capacity of the skeletal muscles. Myokine levels could be a predictive biomarker for evaluating skeletal muscle performance and loss at high altitudes.

The role of sex and ovarian hormones in hippocampal damage and cognitive deficits induced by chronic exposure to hypobaric hypoxia.

PurposeThis study aims to investigate the role of sex and ovarian hormones in hippocampal damage and cognitive deficits and behavioral dysfunction in rats induced by chronic exposure to hypobaric hypoxia.MethodsSix-week-old male and female SD rats were housed for 3 months either in a real altitude (4,250 m) environment as the model of chronic hypobaric-hypoxia (CHH) or in a plain as controls. The animal behavioral and hippocampal neurons at subcellular, molecular, and ultrastructural levels were characterized after CHH exposure.ResultsAfter 3 months of CHH exposure, (1) male CHH rats’ serum testosterone level was lower than male controls’ whereas female CHH rats’ serum estradiol level was higher than female controls’; (2) Morris water maze test finds that male rats showed more learning and spatial memory deficits than female rats; (3) male rats showed more severe hippocampal damage, hippocampal inflammation, oxidative stress and decreased hippocampal integrity (neurogenesis and dendritic spine density) than female rats; (4) Western blot analysis shows that, compared with the male control group, in male CHH group’s hippocampus, expression of nNOS, HO-1, and Bax protein increased whereas that of Bcl-2 protein decreased; (5) Expression of PON2 protein in male rats (CHH and controls) was lower than female rats (CHH and controls). In addition, CHH exposure decreased the expression of PON2 protein in both male and female rats; (6) qPCR analysis reveals that CHH exposure reduced the gene expression of N-methyl-D-aspartate receptor NR2A and NR2B subunits in male rats’ hippocampus. In addition, compared with the sham CHH group, the expression level of PON2 protein decreased in the OVX-CHH group’s hippocampus whereas oxidative stress, neuroinflammation, and degeneration of hippocampal neurons increased in the OVX-CHH group’s hippocampus.ConclusionAfter CHH exposure, male rats were significantly more likely than female rats to develop hippocampal damage, hippocampal neuroinflammation, and cognitive decline and deficits, suggesting that sex and ovarian hormones were significantly involved in regulating the rats’ susceptibility to CHH exposure-induced hippocampal damage.

Effects of Prolonged Exposure to Hypobaric Hypoxia on Oxidative Stress: Overwintering in Antarctic Concordia Station.

Concordia Station is the permanent, research station on the Antarctic Plateau at 3230 m. During the eleventh winter-over campaign (DC11-2015; February 2015 to November 2015) at Antarctic Concordia Station, 13 healthy team members were studied and blood samples were collected at six different time points: baseline measurements (T0), performed at sea level before the departure, and during the campaign at 3, 7, 20, 90, and 300 days after arrival at Concordia Station. Reducing the partial pressure of O2 as barometric pressure falls, hypobaric hypoxia (HH) triggers several physiological adaptations. Among the others, increased oxidative stress and enhanced generation of reactive oxygen/nitrogen species (ROS/RNS), resulting in severe oxidative damage, were observed, which can share potential physiopathological mechanisms associated with many diseases. This study characterized the extent and time-course changes after acute and chronic HH exposure, elucidating possible fundamental mechanisms of adaptation. ROS, oxidative stress biomarkers, nitric oxide, and proinflammatory cytokines significantly increased (range 24-135%) during acute and chronic hypoxia exposure (peak 20th day) with a decrease in antioxidant capacity (peak 90th day: -52%). Results suggest that the adaptive response of oxidative stress balance to HH requires a relatively long time, more than 300th days, as all the observed variables do not return to the preexposition level. These findings may also be relevant to patients in whom oxygen availability is limited through disease (i.e., chronic heart and lung and/or kidney disease) and/or during long-duration space missions.

Association of Peripheral Plasma Neurotransmitters with Cognitive Performance in Chronic High-altitude Exposure

Long-term living at high altitude causes significant impairment of cognitive function. Central neurotransmitters are potential mediators of cognitive performance. We aimed to determine whether there were significant associations between select peripheral plasma neurotransmitters and cognitive performance in humans with chronic high-altitude (HA) exposure and to determine the association between peripheral plasma neurotransmitters and brain neurotransmitters in rats after chronic hypobaric hypoxia (HH) exposure. We demonstrated that 3,4-dihydroxy-L-phenylalanine (DOPA), dopamine, serotonin, 5-hydroxyindole-3-acetic acid (5-HIAA) and GABA in the peripheral plasma were associated with cognitive performance in humans with HA exposure. Consistent with this result, peripheral plasma DOPA, dopamine, serotonin, 5-HIAA and glutamate were associated with brain neurotransmitter levels after chronic HH exposure in rats. These results provide experimental data indicating that neurotransmitter levels and cognitive performance are modified in chronic high-altitude exposure, with a possible causal effect.

NMDA Receptor-Mediated Excitotoxicity Is Involved in Neuronal Apoptosis and Cognitive Impairment Induced by Chronic Hypobaric Hypoxia Exposure at High Altitude.

Ji, Weizhong, Yaqing Zhang, Ri-li Ge, Yaqi Wan, and Jie Liu. NMDA receptor-mediated excitotoxicity is involved in neuronal apoptosis and cognitive impairment induced by chronic hypobaric hypoxia exposure at high altitude. High Alt Med Biol. 22:45-57, 2021. Aim: Exposure to chronic hypobaric hypoxia at high altitude can lead to cognitive impairment; however, its underlying mechanism is still unclear. Excessive expression of glutamate and its receptors can induce excitotoxicity and cause neuronal necrosis, which is an important causative factor for the occurrence of various diseases in the nervous system. Therefore, excitotoxicity may also occur after exposure to a chronic hypobaric hypoxic environment. This study concentrates on the action mechanism of glutamate and its receptor-mediated excitotoxicity in cognitive impairment, induced by chronic hypobaric hypoxic exposure. Methods: Sprague-Dawley rats were fed at regions with three different altitudes (4,300, 2,260, and 450 m) for 8 weeks, and had their behavioral changes assessed by the Morris water maze test. Morphological, molecular biological, and biochemical tests were used to determine the role of N-methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity in neuronal injury and cognitive impairment induced by chronic hypobaric hypoxia exposure. Results: We found that exposure to chronic hypobaric hypoxia at high altitudes could cause cognitive impairment, damage the neurons in the hippocampus and cortex, increase apoptosis, and lead to abnormal Caspase-3 protein expression. The expression of NMDA and a-amino-3-hydroxyl-5-methyl-4-isoxazole acid (AMPA) receptors increased significantly, as did the levels of oxidative stress and free radicals as well. However, no change in cognitive function was observed in the chronic hypobaric hypoxia environment at the middle altitude, there were no statistically significant differences in neuronal apoptosis and related protein expression compared with the rats in the flatland environment group. Conclusion: We show that high-altitude chronic hypobaric hypoxic environment could cause obvious cognitive impairments, which is related to the excitotoxicity mediated by glutamate and its receptors, in contrast to the chronic hypobaric hypoxia environment at middle altitude group and flatland environment group.

Global REACH 2018: The carotid artery diameter response to the cold pressor test is governed by arterial blood pressure during normoxic but not hypoxic conditions in healthy lowlanders and Andean highlanders.

What is the central question of this study? What is the impact of oxygen on the circulatory responses to an isocapnic cold pressor test (CPT) in lowlanders and Andean highlanders? What is the main finding and its importance? Overall, the circulatory responses to an isocapnic CPT were largely unaltered with acute normobaric hypoxia and chronic hypobaric hypoxia exposure in lowlanders. However, the relationship between mean arterial pressure and common carotid artery diameter was dampened in hypoxic conditions. Furthermore, there were no differences in the circulatory responses to the CPT between lowlanders and Andean highlanders with lifelong exposure to high altitude. The impact of oxygen on the circulatory responses to a cold pressor test (CPT) in lowlanders and Andean highlanders remains unknown. Our hypotheses were as follows: (i) in lowlanders, acute normobaric and hypobaric hypoxia would attenuate the common carotid artery (CCA) diameter response to the CPT compared with normobaric normoxia; (ii) Andean highlanders would exhibit a greater CCA diameter response compared with lowlanders; and (iii) a positive relationship between CCA diameter and blood pressure in response to the CPT would be present in both lowlanders and highlanders. Healthy lowlanders (n=13) and Andean highlanders (n=8) were recruited and conducted an isocapnic CPT, which consisted of a 3min foot immersion into water at 0-1°C. Blood pressure (finger photoplethysmography) and CCA diameter and blood flow (Duplex ultrasound) were recorded continuously. The CPT was conducted in lowlanders at sea level in isocapnic normoxic and hypoxic conditions and after 10 days of acclimatization to 4300m (Cerro de Pasco, Peru) in hypoxic and hyperoxic conditions. Andean highlanders were tested at rest at high altitude. The main findings were as follows: (i) in lowlanders, normobaric but not hypobaric hypoxia elevated CCA reactivity to the CPT; (ii) no differences in response to the CPT were observed between lowlanders and highlanders; and (iii) although hypobaric hypoxaemia reduced the relationship between CCA diameter and blood pressure compared with normobaric normoxia (P=0.132), hypobaric hyperoxia improved this relationship (P=0.012), and no relationship was observed in Andean highlanders (P=0.261). These data demonstrate that the circulatory responses to a CPT were modified by oxygen in lowlanders, but were unaltered with lifelong hypoxic exposure.

Muscle sympathetic nerve activity in altitude acclimatized lowlanders during leg cycling exercise

Acute normobaric hypoxia augments muscle sympathetic nerve activity (MSNA) during dynamic cycling exercise; however, the effects of chronic hypobaric hypoxia exposure on this response remain unknown. The purpose of the present study was to determine MSNA reactivity to moderate intensity cycling exercise in lowlanders at sea‐level (344m; Kelowna, BC, Canada) and after 14–21 days of high‐altitude acclimatization (~4300m; Cerro de Pasco, Peru). MSNA (radial microneurography), mean arterial pressure (brachial artery catheter), and heart rate (electrocardiogram) were measured at rest and during cycling exercise (60% of peak workload) in six healthy male participants. Chronic exposure to hypobaric hypoxia increased resting MSNA burst frequency from 14.0 ± 3.2 burst/min at sea‐level, to 38.2 ± 4.5 burst/min (P<0.001). The increase in MSNA during semi recumbent cycling exercise during chronic hypobaric hypoxia exposure was significantly lower compared to sea‐level (Δ MSNA: sea‐level: 106 ± 46% vs. high‐altitude: 43 ± 15% vs; P<0.001). To our knowledge, this is the first investigation to compare MSNA between normobaric normoxia and chronic hypobaric hypoxia during leg cycling exercise. These data indicate that chronic hypobaric hypoxic exposure blunts the relative increase in MSNA during moderate‐intensity dynamic cycling exercise, potentially due to a sympathetic “ceiling” being reached.Support or Funding InformationWilderness Medical Society research in‐training grant (GM)

Characterizing the influence of chronic hypobaric hypoxia on diaphragmatic myofilament contractile function and phosphorylation in high-altitude deer mice and low-altitude white-footed mice.

Deer mice, Peromyscusmaniculatus, live at high altitudes where limited O2 represents a challenge to maintaining oxygen delivery to tissues. Previous work has demonstrated that hypoxia acclimation of deer mice and low altitude white-footed mice (P. leucopus) increases the force generating capacity of the diaphragm. The mechanism behind this improved contractile function is not known. Within myocytes, the myofilament plays a critical role in setting the rate and level of force production, and its ability to generate force can change in response to changes in physiological conditions. In the current study, we examined how chronic hypobaric hypoxia exposure of deer mice and white-footed mice influences the Ca2+ activation of force generation by skinned diaphragmatic myofilaments, and the phosphorylation of myofilament proteins. Results demonstrate that myofilament force production, and the Ca2+ sensitivity of force generation, were not impacted by acclimation to hypobaric hypoxia, and did not differ between preparations from the two species. The cooperativity of the force-pCa relationship, and the maximal rate of force generation were also the same in the preparations from both species, and not impacted by acclimation. Finally, the relative phosphorylation of TnT, and MLC was lower in deer mice than white-footed mice, but was not affected by acclimation. These results indicate that species differences in diaphragm function, and the increase in force production with hypoxia acclimation, are not due to differences, or changes, in myofilament function. However, it appears that diaphragmatic myofilament function in these species is not affected by chronic hypobaric hypoxia exposure.

Proteomic Analysis of Macitentan on Hypoxic Rat Lungs Reveals New Targets for Pulmonary Hypertension Treatment

Background: There are no approved specific therapies for hypoxic pulmonary hypertension (HPH). Although endothelin receptor antagonists (ERAs) have been already used for the treatment of human pulmonary arterial hypertension (PAH), their role in HPH is controversial. Methods: We induced HPH in male Sprague-Dawley rats with chronic hypobaric hypoxia exposure. Proteomic and transcriptomic analyses of lung tissues were carried out and differentially expressed gene products were identified among the control animals, untreated animals and macitentan-treated animals with HPH. Findings: Treatment with the ERA macitentan reduced the PH-related increases in ventricular systolic pressure and mean pulmonary artery pressure, reversed the decrease in pulmonary artery acceleration time, and prevented right ventricular hypertrophy, medial wall thickening and pulmonary arterial muscularization. The bioinformatic analysis revealed that macitentan has two modes of action; macitentan not only restores some proteins to nearly normal levels but also induces the overexpression of some proteins normally expressed at low levels to compensate for their lost functions. We chose one typical potential molecule from each mode and confirmed that WNK inhibition and AMPK activation both significantly ameliorated HPH, alleviated pulmonary vascular remodeling, and attenuated right heart hypertrophy. Interpretation: Our study demonstrates that macitentan has two modes of action and that both modes may be useful for mechanism discovery and the detection of new targets or biomarkers of HPH independent of macitentan. Funding Statement: This work was supported by the National Key Technologies R&D Program for New Drugs of China (2018ZX09J18109-004). Declaration of Interests: The authors declare: None. Ethics Approval Statement: All animal experimental procedures were approved by the Animal Ethics Committee of the Chinese PLA General Hospital and Military Medical College.

Reduced expression of Kalirin-7 contributes to working memory deficit during chronic hypobaric hypoxia exposure

Hypobaric hypoxia (HH) is an environmental stress encountered at high altitude. It has been shown that HH resulted in spine atrophy and working memory deficits. Kalirin-7, a postsynaptic density protein, plays an important and key role in regulating spine dynamics and its plasticity. Spine atrophy is implicated in HH induced memory deficits but role of Kalirin-7 in this phenomenon is not studied. Present study is therefore designed to investigate the effect of chronic HH exposure on Kalirin-7 expression in hippocampus and its role in spatial working memory deficits. Adult rats (n = 12, 3 months old) were exposed to a simulated altitude of 25,000 feet for 7 days. Following HH exposure, spatial working memory was assessed with Radial arm maze and T maze. Hippocampal expression of Kalrin-7 was estimated at mRNA and protein levels. Results of behavioural experiments showed that HH causes significant decrease in the spatial working memory. There was a significant reduction in the protein expression of Kalirin-7 in the hippocampus of hypoxia exposed rats (43.89 ± 7.43) as compared to the control (69.54 ± 10.99). The mRNA expression of Kalrin-7 also exhibits significant reduction (0.59 ± 0.05) in the exposed group as compared to the control (0.98 ± 0.07). Immunohistochemistry showed that Kalirin-7 is decreased significantly in CA1, CA3 and DG regions of the hippocampus. Moreover, memory deficits are significantly correlated with decreased immunoreactivity of the hippocampal Kalirin-7. In conclusion, it can be said therefore, that change in Kalirin-7 expression in the hippocampus is associated with HH induced working memory deficit.

Role of altered proteostasis network in chronic hypobaric hypoxia induced skeletal muscle atrophy.

BackgroundHigh altitude associated hypobaric hypoxia is one of the cellular and environmental perturbation that alters proteostasis network and push the healthy cell towards loss of muscle mass. The present study has elucidated the robust proteostasis network and signaling mechanism for skeletal muscle atrophy under chronic hypobaric hypoxia (CHH).MethodsMale Sprague Dawley rats were exposed to simulated hypoxia equivalent to a pressure of 282 torr for different durations (1, 3, 7 and 14 days). After CHH exposure, skeletal muscle tissue was excised from the hind limb of rats for biochemical analysis.ResultsChronic hypobaric hypoxia caused a substantial increase in protein oxidation and exhibited a greater activation of ER chaperones, glucose-regulated protein-78 (GRP-78) and protein disulphide isomerase (PDI) till 14d of CHH. Presence of oxidized proteins triggered the proteolytic systems, 20S proteasome and calpain pathway which were accompanied by a marked increase in [Ca2+]. Upregulated Akt pathway was observed upto 07d of CHH which was also linked with enhanced glycogen synthase kinase-3β (GSk-3β) expression, a negative regulator of Akt. Muscle-derived cytokines, tumor necrosis factor-α (TNF-α), interferon-ϒ (IFN-©) and interleukin-1β (IL-1β) levels significantly increased from 07d onwards. CHH exposure also upregulated the expression of nuclear factor kappa-B (NF-κB) and E3 ligase, muscle atrophy F-box-1 (Mafbx-1/Atrogin-1) and MuRF-1 (muscle ring finger-1) on 07d and 14d. Further, severe hypoxia also lead to increase expression of ER-associated degradation (ERAD) CHOP/ GADD153, Ub-proteasome and apoptosis pathway.ConclusionsThe disrupted proteostasis network was tightly coupled to degradative pathways, altered anabolic signaling, inflammation, and apoptosis under chronic hypoxia. Severe and prolonged hypoxia exposure affected the protein homeostasis which overwhelms the muscular system and tends towards skeletal muscle atrophy.

Global hypoxia induced impairment in learning and spatial memory is associated with precocious hippocampal aging

Both chronological aging and chronic hypoxia stress have been reported to cause degeneration of hippocampal CA3 neurons and spatial memory impairment through independent pathways. However, the possible occurrence of precocious biological aging on exposure to single episode of global hypoxia resulting in impairment of learning and memory remains to be established. The present study thus aimed at bridging this gap in existing literature on hypoxia induced biological aging. Male Sprague Dawley rats were exposed to simulated hypobaric hypoxia (25,000ft) for different durations and were compared with aged rats. Behavioral studies in Morris Water Maze showed decline in learning abilities of both chronologically aged as well as hypoxic rats as evident from increased latency and pathlength to reach target platform. These behavioral changes in rats exposed to global hypoxia were associated with deposition of lipofuscin and ultrastructural changes in the mitochondria of hippocampal neurons that serve as hallmarks of aging. A single episode of chronic hypobaric hypoxia exposure also resulted in the up-regulation of pro-aging protein, S100A9 and down regulation of Tau, SNAP25, APOE and Sod2 in the hippocampus similar to that in aged rats indicating hypoxia induced accelerated aging. The present study therefore provides evidence for role of biological aging of hippocampal neurons in hypoxia induced impairment of learning and memory.

Evaluation of hepatic metabolism and pharmacokinetics of ibuprofen in rats under chronic hypobaric hypoxia for targeted therapy at high altitude

With studies indicative of altered drug metabolism and pharmacokinetics (DMPK) under high altitude (HA)-induced hypobaric hypoxia, consideration of better therapeutic approaches has continuously been aimed in research for HA related illness management. DMPK of drugs like ibuprofen may get affected under hypoxia which establishes the requirement of different therapeutic dose regimen to ensure safe and effective therapy at HA. This study examined the effects of the chronic hypobaric hypoxia (CHH) on hepatic DMPK of ibuprofen in rats. Experimental animals were exposed to simulated altitude of 7620m (∼25,000ft) for CHH exposure (7 or 14 days) in decompression chamber and administered with ibuprofen (80mg/kg, body weight, p.o.). Results demonstrated that CHH significantly altered PK variables of ibuprofen and activities of both phase-I and II hepatic metabolic enzymes as compared to the animals under normoxic conditions. Hepatic histopathological observations also revealed marked alterations. Increase in pro-inflammatory cytokines/chemokines viz. IL-1β, IL-2, IFN-γ, TNF-α exhibited close relevance with diminished CYP2C9 expression under CHH. Moreover, the down-regulated CYP2C9 level further supported the underlying mechanism for reduced metabolism of ibuprofen and as a result, increased retention of parent drug in the system. Increased mean retention time, Vd, T½ of ibuprofen, and decreased AUC, Cmax and clearance during CHH further strengthened the present findings. In conclusion, CHH exposure significantly affects hepatic DMPK of ibuprofen, which may further influence the usual therapeutic dose-regimen. Further, there is requirement of human studies to evaluate their susceptibility toward hypobaric hypoxia.

Proteome profiling of hippocampus during chronic hypobaric hypoxia exposure: Enriched environment as a therapeutic approach

Event Abstract Back to Event Proteome profiling of hippocampus during chronic hypobaric hypoxia exposure: Enriched environment as a therapeutic approach Vishal Jain1*, Shashi B. Singh1 and Govindasamy Ilavazhagan2 1 Defence Institute of Physiology and Allied Sciences, Department of Neurophysiology, India 2 Hindustan University, Research, India Hypobaric hypoxia (HH) is known to cause cognitive dysfunctions owing to the high oxygen dependency of the brain. Cognitive and motor deficits have been reported to occur on chronic exposure to HH. On the other hand enriched environment (EE) enhances learning and memory, reduces memory decline during different neurological disorders. Previously we have shown that enriched environment improves cognition and decreases neurodegeneration during chronic exposure to hypobaric hypoxia. Present study is designed to explore the effect of enriched environment on hypobaric hypoxia induced alteration in synaptic plasticity and strength. Sprague dawley rats (3 months old) were exposed to hypobaric hypoxia condition in an animal decompression chamber at an altitude of 25000 feet for continuous 7 days. Animals from control group were kept in standard cage whereas enriched group were kept in EE cage. Following exposure rats were sacrificed and hippocampi was dissected out and processed for different experimental protocols. MALDI following 2D electrophoresis was performed to study the global change in hippocampal protein expression. Further expression of different synaptic proteins was assessed through western blotting and immunohistochemistry. Golgi stain was performed to study dendritic arbrorization. Results of the present study showed that identified proteins belong to a diverse variety of functional classes including cell death, proteins involved in oxidative stress metabolism, synaptic proteins, growth factors and proteins associated with signalling. Hypobaric hypoxia decreases expression of synaptic proteins i.e. synaptophysin, PSD-95, synaptotagmin which further validated by western blotting whereas exposing them in enriched environment ameliorate this synaptic loss. Golgi staining reveals increased dendritic arborization, spine density and morphology on exposure to EE during HH. Present study also reveals the possible role of BDNF/TrkB signalling in enriched environment mediated modulation hippocampal synaptic plasticity. Therefore it can be concluded that enriched environment ameliorate HH induced synaptic loss through BDNF/TrkB signalling. Keywords: Synaptophysin, hypoxia, PSD-95, synaptotagmin, BDNF/TrkB signalling Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: YIC02: Young Investigator Colloquium 2 Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Jain V, Singh SB and Ilavazhagan G (2016). Proteome profiling of hippocampus during chronic hypobaric hypoxia exposure: Enriched environment as a therapeutic approach. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00059 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Dr. Vishal Jain, Defence Institute of Physiology and Allied Sciences, Department of Neurophysiology, Delhi, Delhi, India, vishal6784@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Vishal Jain Shashi B Singh Govindasamy Ilavazhagan Google Vishal Jain Shashi B Singh Govindasamy Ilavazhagan Google Scholar Vishal Jain Shashi B Singh Govindasamy Ilavazhagan PubMed Vishal Jain Shashi B Singh Govindasamy Ilavazhagan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Koroška 8000: digit responses to cold stress following himalayan expedition to broadpeak, Pakistan (8051 m)

We investigated the effects chronic hypobaric hypoxia exposure would have on alpinists' physiological adaptations, including: aerobic fitness, body composition, haematological variables and digit perfusion responses to cold stress, performed before and immediately after a 35 day high altitude climbing expedition.

Protective role of HSF1 and HSP70 in rat testis apoptotic cells exposed to chronic hypobaric hypoxia

High altitude exposure is an unusual situation. However, this phenomenon is frequently found in the north of Chile, thanks to the continuous movement of mining workers at the Cordillera de los Andes. In rat testis, this condition known as chronic hypobaric hypoxia (CHH) induces oxidative stress and hyperthermia, conducing to apoptosis and hypospermatogenesis. The main objective of this work was to evaluate the expression of HSP70 and HSF1 in the spermatogenic stages in front of thermal stress induced by CHH and also to determine the apoptotic level. Teen-weeks-old male Wistar rats were exposed to normoxia and CHH, corresponding to 4600 m of simulated altitude for a period of 5, 15 and 30 days. Immunohistochemistry and western blot showed a significative and progressive increase in HSP70 expression in spermatogonias, spermatocytes and Sertoli cells along the exposure time. The transcription factor expression HSF1 in testis was also increased in CHH, but it was decreased after 30 days. Finally, apoptosis was increased in spermatogonias, spermatocytes and spermatids but decreased after 15 days in spermatids and after 30 days in spermatogonias and spermatocytes. In conclusion, testicular hyperthermia induced by the CHH exposure conduces to increase HSF1 and HSP70 expression, protecting cell integrity and attenuating the apoptotic effect induced by this condition. By grant: INNOVA CORFO-Chile 06FCO11BC-118

Time Course of Endocrine Changes in the Hypophysis-Gonad Axis Induced by Hypobaric Hypoxia in Male Rats

Chronic hypobaric hypoxia (CHH) induces a decrease in sperm output and spermatogenesis in male rats. The mechanisms that underlie these changes in testicular function are unknown and could involve changes in the hypophysis-gonad axis. We have tested the hypothesis that changes take place in the endocrine status (FSH, follicle stimulating hormone; LH, luteinizing hormone; testosterone) of rats subjected to CHH. Male Wistar rats were maintained under normobaric or hypobaric conditions (428 torr, 4,600 m). On days 0, 5, 15 and 30 post-exposure, 12 rats were anesthetized, their body weights were measured and blood samples were collected. The testicles were fixed in 4% formaldehyde and processed for histological analysis. In this time course, the FSH levels rose by day 5 post-exposure. On subsequent days, the FSH levels decreased in rats subjected to CHH with a tendency to remain higher than the normoxic group. The LH plasma levels decreased in rats exposed to CHH. Consistent with the decrease in LH levels, the plasma testosterone level decreased significantly after 30 days of CHH exposure. Integrated analysis of hormonal changes in rats subjected to CHH and the body dehydration that occurs in HH allows us to conclude that the effects of CHH on spermatogenesis may be partially related to changes in the hypophysis-gonad hormonal axis.

Acetyl- l-Carnitine ameliorates hypobaric hypoxic impairment and spatial memory deficits in rats

Inadequate oxygen availability at high altitude causes oxidative stress and generation of reactive oxygen species, which may lead to memory impairment. Hippocampus, which plays a key role in the learning and memory processes, is especially vulnerable to hypoxic damage. The present study was aimed at investigating the effect of Acetyl- l-Carnitine on spatial working and reference memory deficits along with oxidative and apoptotic damage, caused by hypobaric hypoxia in male Sprague Dawley rats. Rats were trained in Morris Water Maze for eight days after which they were submitted to chronic hypobaric hypoxia exposure at a simulated altitude of 6100 m for three days. Rats received daily Acetyl- l-Carnitine at a dosage of 75 mg/kg body weight orally during exposure. Subsequent to exposure, performance of the animals was tested in Morris Water Maze, which revealed working memory impairment that was significantly improved by Acetyl- l-Carnitine. However, there was no change in the reference memory after hypobaric hypoxia exposure. Following behavioral study animals were sacrificed and biomarkers of oxidative damage like free radical production, lactate dehydrogenase activity, lipid peroxidation, antioxidant status and expression of apoptotic [viz. caspase-3, Apoptosis activating factor (Apaf-1), bax, cytochrome c] and anti-apoptotic protein-Bcl-2 were studied in the hippocampus. There was a significant increase in oxidative stress along with increased expression of apoptotic proteins and NR1 subunit of glutamate receptor indicating occurrence of excitotoxicity in hypoxia exposed rats. These results suggested that supplementation with Acetyl- l-Carnitine improves spatial working memory deficits reduces oxidative stress and inhibits apoptotic cascade induced by hypoxia.