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Browsing by Autor "Edith M. Schneider Gasser"

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    Coping with hypoxemia: Could erythropoietin (EPO) be an adjuvant treatment of COVID-19?
    (Elsevier BV, 2020) Jorge Soliz; Edith M. Schneider Gasser; Christian Arias‐Reyes; Fernanda Aliaga‐Raduán; Liliana Poma-Machicao; Gustavo Zubieta‐Calleja; Werner I. Furuya; Pedro Trevizan‐Baú; Rishi R. Dhingra; Mathias Dutschmann
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    Decreased incidence, virus transmission capacity, and severity of COVID-19 at altitude on the American continent
    (2020) Christian Arias‐Reyes; Favio Carvajal-Rodriguez; Liliana Poma-Machicao; Fernanda Aliaga-Raudan; Danuzia A. Marques; Natalia Zubieta DeUrioste; Roberto A. Accinelli; Edith M. Schneider Gasser; Gustavo Zubieta‐Calleja; Mathias Dutschmann
    Abstract The coronavirus disease 2019 (COVID-19) outbreak in North, Central, and South America has become the epicenter of the current pandemic. We have suggested previously that the infection rate of this virus might be lower in people living at high altitude (over 2,500 m) compared to that in the lowlands. Based on data from official sources, we performed a new epidemiological analysis of the development of the pandemic in 23 countries on the American continent as of May 23, 2020. Our results confirm our previous finding, further showing that the incidence of COVID-19 on the American continent decreases significantly starting at 1,000 m above sea level (masl). Moreover, epidemiological modeling indicates that the virus transmission rate capacity is lower in the highlands (>1,000 masl) than in the lowlands (<1,000 masl). Finally, evaluating the differences in the recovery percentage of patients, the death-to-case ratio, and the theoretical fraction of undiagnosed cases, we found that the severity of COVID-19 is also decreased above 1,000 m. We conclude that the impact of the COVID-19 decreases significantly with altitude. Highlights There is a negative correlation between altitude and COVID-19 incidence on the American Continent starting from 1,000 m above sea level. The transmission rate of SARS-CoV-2 is lower in the highlands than in the lowlands. The severity of COVID-19 decreases significantly with increased altitude.
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    Developmental expression patterns of erythropoietin and its receptor in mouse brainstem respiratory regions
    (Elsevier BV, 2019) Edith M. Schneider Gasser; Elizabeth Elliot‐Portal; Christian Arias‐Reyes; Karen Losantos-Ramos; Kasifa Khalid; Omolara O. Ogunshola; Jorge Soliz
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    Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude?
    (Elsevier BV, 2020) Christian Arias‐Reyes; Natalia Zubieta-DeUrioste; Liliana Poma-Machicao; Fernanda Aliaga‐Raduán; Favio Carvajal-Rodriguez; Mathias Dutschmann; Edith M. Schneider Gasser; Gustavo Zubieta‐Calleja; Jorge Soliz
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    High altitude induces a shift from complex I to complex II in the brain mitochondria of newborn and adult mice
    (The Company of Biologists, 2025) Maud Demarest; Fernanda Aliaga‐Raduán; Christian Arias‐Reyes; Marcelino Gonzales; Edith M. Schneider Gasser; Jorge Soliz; Vincent Joseph
    Species living at high altitude (HA) often exhibit optimized oxygen utilization at adulthood; however, the plasticity of metabolic pathways during postnatal development remains unclear. Because mice, but not rats, are commonly found at HA, we investigated mitochondrial oxygen consumption rates (OCR) in the cerebral cortex of both species across postnatal development and at adulthood at sea level (SL; Quebec, Canada) under normoxia or hypoxia (13.5% O2), and at HA (La Paz, Bolivia, 3600 m) after 50 generations of residency. At postnatal day (P)7, P14 and P21 and in adults (P60-90), fresh tissue samples were used to assess mitochondrial OCR under states of proton LEAK (OCRLEAK(N)) and oxidative phosphorylation (OXPHOS) using substrates for complex I (N pathway - OCRN), complex II (S pathway - OCRS) and complexes I+II (NS pathways - OCRNS). Our results showed: (1) at HA, rats exhibit higher OCR at P7, P14 and adulthood compared with their SL counterparts, and (2) HA residency induces a shift from the N pathway to the S pathway at all ages in mice. Finally, these responses were absent in SL animals exposed to postnatal hypoxia, highlighting the importance of studying HA-living species. These findings emphasize key metabolic shifts, with implications for understanding responses to hypoxia in species showing divergent success at HA.
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    Hypercapnic ventilatory response is decreased in a mouse model of excessive erythrocytosis
    (American Physiological Society, 2016) Sofien Laouafa; Elizabeth Elliot‐Portal; Susana Revollo; Edith M. Schneider Gasser; Vincent Joseph; Nicolas Voituron; Max Gassmann; Jorge Soliz
    The impact of cerebral erythropoietin (Epo) in the regulation of the hypercapnic ventilatory response (HcVR) is controversial. While we reported that cerebral Epo does not affect the central chemosensitivity in C57Bl6 mice receiving an intracisternal injection of sEpoR (the endogenous antagonist of Epo), a recent study in transgenic mice with constitutive high levels of human Epo in brain and circulation (Tg6) and in brain only (Tg21), showed that Epo blunts the HcVR, maybe by interacting with central and peripheral chemoreceptors. High Epo serum levels in Tg6 mice lead to excessive erythrocytosis (hematocrit ~80-90%), the main symptom of chronic mountain sickness (CMS). These latter results support the hypothesis that reduced central chemosensitivity accounts for the hypoventilation observed in CMS patients. To solve this intriguing divergence, we reevaluate HcVR in Tg6 and Tg21 mouse lines, by assessing the metabolic rate [O consumption (V̇) and CO production (V̇)], a key factor modulating ventilation, the effect of which was not considered in the previous study. Our results showed that the decreased HcVR observed in Tg6 mice (~70% reduction; < 0.01) was due to a significant decrease in the metabolism (~40%; < 0.0001) rather than Epo's effect on CO chemosensitivity. Additional analysis in Tg21 mice did not reveal differences of HcVR or metabolism. We concluded that cerebral Epo does not modulate the central chemosensitivity system, and that a metabolic effect upon CO inhalation is responsible for decreased HcVR observed in Tg6 animals. As CMS patients also show decreased HcVR, our findings might help to better understand respiratory disorders at high altitude.
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    Living at high altitude induces a switch from complex I to complex II in hepatic mitochondria of mice during postnatal development
    (American Physiological Society, 2025) Maud Demarest; Fernanda Aliaga‐Raduán; Marcelino Gonzales; Edith M. Schneider Gasser; Jorge Soliz; Vincent Joseph
    Living at high altitude (HA) requires physiological and metabolic adjustments to sustain adequate homeostasis. Mitochondria play a key role in these adaptation processes as it consumes &gt;85% of cellular O 2 to produce energy. In adults, HA hypoxia can induce structural changes in the electron transport chain (ETC) to optimize the use of O 2 . In newborn, postnatal development at HA results in slower growth rate and delayed development for some important homeostatic functions. While there is evidence that in species adapted to HA O 2 utilization is optimized, potential underlying plasticity of metabolic pathways during postnatal development is unknown. Because we already demonstrated that FVB mice are a good model to study HA adaptation, we used this laboratory strain to evaluate mitochondrial O 2 consumption rates (OCR) of liver samples during postnatal development and at adulthood at sea level (SL - Quebec, Canada) and in animals that have been raised at HA for &gt;50 generations (La Paz, Bolivia, 3600m). Using the high-resolution oxygraph Oroboros O2k, we measured OCR in mice at postnatal day 7 (P7), 14 (P14), 21 (P21) and 60 (adults – P60) under states of maximum capacity (ET) with substrates for complex I (ET N – pyruvate, malate, glutamate), complex II (ET S – succinate), or I + II (maximal OCR - ET NS ). Our results show that ET N was considerably reduced at all ages in HA compared to SL mice (P7, -92%; P14, -86%; P21, -87%). Contrastingly, ET S was 32% higher in HA P21 mice while it was 30% lower in HA adults compared to SL. No difference was found for ET NS during postnatal development, but values were lower in HA adults compared with SL (101 ± 26 vs 167 ± 43 pmol/s*mg). We also calculated the relative contribution of CI and CII to maximal OCR (ET NS ). While CI contribution was substantially lower at all ages in HA mice compared to SL, CII participation was higher at P7 (+41%), P14 (+14%) and P21 (+16%) but was unchanged at adulthood. These results suggest that at HA, a development shift occurs from CI to CII, allowing maximal OCR (ET NS ) to remain unchanged between HA and SL. This shift might be a protective mechanism since the activity of CII is only dependent on the availability of its substrate (succinate), while CI is more sensitive to decreases in intracellular O 2 . This reprogramming was absent in adults; both CI and CII activity decreased at HA compared to SL. These differences highlight the distinct effect of HA hypoxia at different life stages. Funded by NSERC. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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    Nocturnal Sleep Breathing Patterns in Healthy Adolescents Residing at Very High Altitudes in Bolivia
    (Wiley, 2026) Keaton Patterson; Santiago Ucrós Rodríguez; E. Nicolás Arancibia‐Levit; Fernanda Aliaga Raduan; José Antonio Viruez Soto; Max Gassmann; Silvia Ulrich; Michael Furian; Edith M. Schneider Gasser
    Data on sleep and respiratory patterns among adolescents residing at very high altitude (> 3500 m) remain scarce, and altitude-related physiological differences may influence these parameters. Studying adolescents at different very high altitudes is crucial, as subtle environmental variations could affect sleep-related oxygenation and respiratory function. This study aimed to characterise sleep-related oxygenation and respiratory parameters in healthy adolescents native to two distinct very high-altitude environments. Overnight sleep polygraphy was performed in 163 healthy adolescents aged 13.5 to < 18 years living in La Paz (3620 m) and El Alto (4060 m), Bolivia. Mean nocturnal oxygen saturation, oxygen desaturation index, and apnea-hypopnea index were assessed alongside subjective sleep quality, morning blood pressure, heart rate, haemoglobin concentration, and Epworth Sleepiness Scale scores. Adolescents at 4060 m had significantly lower mean nocturnal oxygen saturation (84.8% ± 2.2%) compared with those at 3620 m (87.8% ± 1.8%), and a higher oxygen desaturation index (21.2 ± 8.5/h vs. 17.1 ± 9.0/h). The apnea-hypopnea index did not differ significantly between altitudes (6.2 ± 4.8/h vs. 5.6 ± 4.6/h). At 3620 m, females showed lower oxygen desaturation and apnea-hypopnea indices compared with males. Despite the more pronounced nocturnal hypoxemia at 4060 m, haemoglobin concentration did not increase, suggesting limited haematological compensation. Subjective sleep quality, blood pressure, and heart rate were similar between both altitude groups. Healthy adolescents living chronically at very high altitude exhibit altitude-dependent reductions in nocturnal oxygenation and increased desaturation frequency, without evidence of sleep-disordered breathing. These findings underscore the need for altitude-specific normative values to support accurate interpretation of sleep studies in high-altitude populations.
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    Plasticity of mitochondrial proton leak in adults and newborn mice as a possible strategy for high altitude adaptation
    (Elsevier BV, 2024) Maud Demarest; Fernanda Aliagia-Raduan; Pablo Iturri; Christian Arias‐Reyes; Edith M. Schneider Gasser; Jorge Soliz; Vincent Joseph

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