Browsing by Autor "Vincent Joseph"

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Altered thermal and metabolic control in newborn rats at high altitude
(Wiley, 2008) Vincent Joseph; Jorge Soliz; Max Gassmann; Marcelino Gonzales Isidro; Enrique Vargas; Rudy Soria
In acute hypoxia, newborn reduce oxygen consumption (VO2) and rectal temperature (Tr), but it remains unclear if these responses are maintained in chronic hypoxia. We used rats living at high altitude (3600 m, La Paz Bolivia) at postnatal days 7–8 (P7, n=5, body weight 13±1 g) and 15–16 (P15, n=6, 21±1 g). Tr and VO2 were measured in 21%O2 (room air), 35%O2 (sea level PO2), and 10%O2 (hypoxia), during 20 minutes each. Ambient temperature (Ta) was 34°C at P7 and 30°C at P15. Tr‐Ta was used as an index of thermoregulatory control. At P7, Tr‐Ta was −0.1±0.2°C, suggesting that thermoregulatory control is not established. In 35%O2, Tr was 34.8±0.2°C, and 32.0±0.6°C in 10%O2. At P15, Tr‐Ta was 5.2±0.2°C in room air, Tr did not increased in 35%O2, and was 31.8±0.4°C in 10%O2. VO2 was high (P7=8.6±0.8; P15=9.4±0.4 ml/min/100g) compared to sea level rats (5 ml/min/100g in 20g P10 rats). In P7 and P15 rats, VO2 increased in 35%O2 and dropped in 10%O2. Our results suggest that chronic hypoxia delays the establishment of thermoregulation and increases metabolic rate in newborn rats. The drop of Tr and VO2 in 10%O2 were however well maintained. Founded by NSERC
Comparative responses of arterial oxygen saturation and heart rate during postnatal development in rats living at high and low altitude.
(Wiley, 2013) A. Lemoine; Gabriella Villalpando; Marcelino Gonzales; Rudy Soria; Vincent Joseph
We used pulse oximetry to measure arterial oxygen saturation (SpO2) and heart rate (HR) in 4 and 14 day‐old rats raised at HA (La Paz, Bolivia, 3,600 m/12,000ft) or at sea level (SL, Québec, Canada). SpO2 and HR were measured at 5 different levels of inspired PO2 (PiO2: 160 ‐ 60 mmHg – 10 min each), in awake rats maintained in a chamber flushed with room air or the desired gas mixtures. When exposed to a PiO2 of 160 mmHg, P4 HA rats had a similar SpO2 than P4 SL, but a lower HR. At lower PiO2, HA rats maintained a much higher SpO2 than SL rats. HR increased in HA rats (but not in SL rats) at low PiO2. Contrastingly, P14 HA rats exposed to a PiO2 of 160 mmHg had a lower SpO2 than SL (93.7±1.1% vs. 98.8±0.1%, p<0.0001), and similar SpO2 at lower PiO2. HR was higher in P14 HA rats vs. SL rats at all PiO2 levels. A group of SL rats was raised in hypoxia (13.5% O2 – similar to HA PiO2) between P4 and P14. This reduces SpO2 values measured at PiO2 below 160 mmHg, and enhances HR. Male and female rats had similar responses. We conclude that: a) 4‐day old rats raised at HA had efficient responses that help maintaining a high SpO2 under a wide range of PiO2 ‐ b) these responses are no longer apparent in P14. Since rats are not found under natural conditions at HA, success to develop adequate responses to hypoxia during early postnatal development might be critical for genetic adaptation to altitude. Founded by NSERC.
Complex II‐linked mitochondrial respiration is upregulated during postnatal development in high‐altitude grown mice
(Wiley, 2022) Christian Arias‐Reyes; Fernanda Aliaga‐Raduán; Oscar M. Rollano‐Peñaloza; Pablo Iturri; Jorge Soliz; Vincent Joseph
Recently, we have shown that chronic normobaric hypoxia (12% O 2 – 21 days) triggers mitochondrial and cell‐ metabolic plasticity in the retrosplenial cortex of male adult FVB mice but not in SD rats. In these animals we reported a transient upregulation of anaerobic metabolic pathways (glycolysis + lactate metabolism) followed by an attenuation in the mitochondrial respiration. These results pointed to an optimized use of oxygen at cellular level in an area of the brain responsible of processing visual information and spatial memory. Features of great importance in the biological fitness. In the current work we investigate how the residence in high altitude (La Paz – Bolivia, 3,600 m) affects the developmental profile of the mitochondrial respiratory efficiency in the retrosplenial cortex of mice and rats. We hypothesize that the mitochondrial plasticity observed in adult mice will have a process of maturation during postnatal development. This response shall be absent in rats. To do so, we measured the mitochondrial oxygen consumption rate (OCR) in saponin‐permeabilized brain samples from FVB mice and SD rats born and grown in La Paz. The animals were sacrificed at postnatal ages p7, p14, p21, and adulthood (P90), and the OCR linked to the use of NADH (N pathway), FADH 2 (S pathway), or both (NS pathway) was quantified by means of high‐resolution respirometry (OROBOROS). Our results show a pattern of maturation (increase) of the mitochondrial respiration in the retrosplenial cortex along with the postnatal development (21 days+) of mice and rats. However, an upregulation of the participation of the S pathway (complex II‐linked) in the mitochondrial respiration was observed during the first three weeks of age only in mice. This observation supports previous works suggesting a key role of the complex II and succinate (substrate of complex II) in the successful cellular and mitochondrial acclimatization to hypoxia. These findings contribute to further establish FVB mice and SD rats as a model to study divergent acclimatization to hypoxia.
Divergent Mitochondrial Antioxidant Activities and Lung Alveolar Architecture in the Lungs of Rats and Mice at High Altitude
(Frontiers Media, 2018) Alexandra Jochmans‐Lemoine; Susana Revollo; Gabriella Villalpando; I. Valverde; Marcelino Gonzales; Sofien Laouafa; Jorge Soliz; Vincent Joseph
Compared with mice, adult rats living at 3,600 m above sea level (SL-La Paz, Bolivia) have high hematocrit, signs of pulmonary hypertension, and low lung volume with reduced alveolar surface area. This phenotype is associated with chronic mountain sickness in humans living at high altitude (HA). We tested the hypothesis that this phenotype is associated with impaired gas exchange and oxidative stress in the lungs. We used rats and mice (3 months old) living at HA (La Paz) and SL (Quebec City, Canada) to measure arterial oxygen saturation under graded levels of hypoxia (by pulse oximetry), the alveolar surface area in lung slices and the activity of pro- (NADPH and xanthine oxidases-NOX and XO) and anti- (superoxide dismutase, and glutathione peroxidase-SOD and GPx) oxidant enzymes in cytosolic and mitochondrial lung protein extracts. HA rats have a lower arterial oxygen saturation and reduced alveolar surface area compared to HA mice and SL rats. Enzymatic activities (NOX, XO, SOD, and GPx) in the cytosol were similar between HA and SL animals, but SOD and GPx activities in the mitochondria were 2-3 times higher in HA vs. SL rats, and only marginally higher in HA mice vs. SL mice. Furthermore, the maximum activity of cytochrome oxidase-c (COX) measured in mitochondrial lung extracts was also 2 times higher in HA rats compared with SL rats, while there was only a small increase in HA mice vs. SL mice. Interestingly, compared with SL controls, alterations in lung morphology are not observed for young rats at HA (15 days after birth), and enzymatic activities are only slightly altered. These results suggest that rats living at HA have a gradual reduction of their alveolar surface area beyond the postnatal period. We can speculate that the elevation of SOD, GPx, and COX activities in the lung mitochondria are not sufficient to compensate for oxidative stress, leading to damage of the lung tissue in rats.
Divergent physiological responses in laboratory rats and mice raised at high altitude
(The Company of Biologists, 2015) Alexandra Jochmans‐Lemoine; Gabriella Villalpando; Marcelino Gonzales; I. Valverde; Rudy Soria; Vincent Joseph
Ecological studies show that mice can be found at high altitude (HA - up to 4000 m) while rats are absent at these altitudes, and there are no data to explain this discrepancy. We used adult laboratory rats and mice that have been raised for more than 30 generations in La Paz, Bolivia (3600 m), and compared their hematocrit levels, right ventricular hypertrophy (index of pulmonary hypertension) and alveolar surface area in the lungs. We also used whole-body plethysmography, indirect calorimetry and pulse oxymetry to measure ventilation, metabolic rate (O2 consumption and CO2 production), heart rate and pulse oxymetry oxygen saturation (pO2 ,sat) under ambient conditions, and in response to exposure to sea level PO2 (32% O2=160 mmHg for 10 min) and hypoxia (18% and 15% O2=90 and 75 mmHg for 10 min each). The variables used for comparisons between species were corrected for body mass using standard allometric equations, and are termed mass-corrected variables. Under baseline, compared with rats, adult mice had similar levels of pO2 ,sat, but lower hematocrit and hemoglobin levels, reduced right ventricular hypertrophy and higher mass-corrected alveolar surface area, tidal volume and metabolic rate. In response to sea level PO2 and hypoxia, mice and rats had similar changes of ventilation, but metabolic rate decreased much more in hypoxia in mice, while pO2 ,sat remained higher in mice. We conclude that laboratory mice and rats that have been raised at HA for >30 generations have different physiological responses to altitude. These differences might explain the different altitude distribution observed in wild rats and mice.
Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in female rats
(American Physiological Society, 2002) Vincent Joseph; Jorge Soliz; Ruddy Soria; Jacqueline Pequignot; R. Favier; Hilde Spielvogel; Jean Marc Pequignot
We tested the hypothesis that ovarian steroids stimulate breathing through a dopaminergic mechanism in the carotid bodies. In ovariectomized female rats raised at sea level, domperidone, a peripheral D2-receptor antagonist, increased ventilation in normoxia (minute ventilation = +55%) and acute hypoxia (+32%). This effect disappeared after 10 daily injections of ovarian steroids (progesterone + estradiol). At high altitude (3,600 m, Bolivian Institute for High-Altitude Biology-IBBA, La Paz, Bolivia), neutered females had higher carotid body tyrosine hydroxylase activity (the rate-limiting enzyme for catecholamine synthesis: +129%) and dopamine utilization (+150%), lower minute ventilation (-30%) and hypoxic ventilatory response (-57%), and higher hematocrit (+18%) and Hb concentration (+21%) than intact female rats. Consistent signs of arterial pulmonary hypertension (right ventricular hypertrophy) also appeared in ovariectomized females. None of these parameters was affected by gonadectomy in males. Our results show that ovarian steroids stimulate breathing by lowering a peripheral dopaminergic inhibitory drive. This process may partially explain the deacclimatization of postmenopausal women at high altitude.
Erythropoietin and caffeine exert similar protective impact against neonatal intermittent hypoxia: Apnea of prematurity and sex dimorphism
(Elsevier BV, 2019) Sofien Laouafa; Pablo Iturri; Christian Arias‐Reyes; François Marcouiller; Marcelino Gonzales; Vincent Joseph; Aïda Bairam; Jorge Soliz
Gender differentiation of the chemoreflex during growth at high altitude: functional and neurochemical studies
(American Physiological Society, 2000) Vincent Joseph; Jorge Soliz; J. M. Pequignot; B. Semporé; J. M. Cottet-Émard; Y. Dalmaz; R. Favier; Hilde Spielvogel; J. M. Pequignot
The effect of chronic hypoxia on gender differences in physiology and neurochemistry of chemosensory pathways was studied in prepubertal and adult rats living at sea level (SL; Lyon, France) or at high altitude (HA; La Paz, Bolivia, 3,600 m). HA adult rats had higher hematocrit (Ht%), Hb concentration, resting ventilatory rate (Ve(100)), and higher tyrosine hydroxylase (TH) activity in carotid bodies (CB) than SL animals. At HA and SL, adult females had lower Ht% (46.0 +/- 0.8 vs. 50.4 +/- 0.6% at HA, P < 0.05 and 43.8 +/- 0.9 vs. 47.1 +/- 0.8% at SL, P < 0.05) and Hb (16.1 +/- 0.3 vs. 17.7 +/- 0.2 g/dl at HA, P < 0.05 and 14.5 +/- 0.3 vs. 15.6 +/- 0.1 g/dl at SL, P < 0.05) than males. Females had higher Ve(100) [170 +/- 19 vs. 109 +/- 7 ml. min(-1). 100 g(-1) at HA, P < 0.05 and 50 +/- 3 vs. 40 +/- 2 ml. min(-1). 100 g(-1) at SL, not significant (NS)] and lower CB-TH activity (1.40 +/- 0.2 vs. 3.87 +/- 0.6 pmol/20 min at HA, P < 0.05 and 0.52 +/- 0.1 vs. 0.68 +/- 0.1 pmol/20 min at SL; NS) than males at HA only. The onset of hypoxic ventilatory response during development was delayed at HA. Prepubertal HA females had higher Ve(100) than males (2 wk old, +47%) and higher CB-TH activity (3 wk old, +51%). Medullary noradrenergic groups were sex dimorphic during development at SL. Rats raised at HA had a drop of TH activity between the second and the third postnatal week in all medullary groups. In conclusion, our data support the hypothesis that the CB is the major site for sexual differentiation of the ventilatory control. Ventilatory differences appeared before puberty, and the animals bred at HA had profound alterations in the developmental process of the chemoreflex and its neural pathways. Some of these alterations are under dependence of the sex of the animal, and there is an important interaction between gender and the hypoxic environmental condition during the developmental period.
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.
Higher metabolic capacity in mice in comparison to rats during acclimation to chronic hypoxia
(Wiley, 2019) Christian Arias Reyes; Karen Losantos; Jorge Soliz; Vincent Joseph
The aptitude of mammals to colonize high altitude (HA) environments is limited by their ability to tolerate decreased oxygen availability. While rats are not found under natural conditions above 2500 meters of altitude, mice are common in such habitats. Previous research in our lab showed that rats and mice display divergent physiological and molecular responses after acute (short‐term) exposure to hypoxia. As the response to hypoxia and metabolism control are tightly linked, in this work we aimed to identify the strategies underlying the metabolic response of mice and rats along the process of acclimation to short and long‐term hypoxia. Male FVB mice and Sprague – Dawley rats were exposed to hypoxia (12% O 2 ) for 0 hours (normoxic controls), 6 hours, 1, 7 and 21 days. During the last hour of the exposure, the whole‐body oxygen consumption (VO 2 ) and CO 2 production (VCO 2 ) were measured by indirect calorimetry. In following, samples of brain cortex were collected to evaluate the mitochondrial O 2 consumption rate with the high‐resolution respirometer Oxygraph‐2k (Oroboros Inc.). Our results in mice showed increased VO 2 and VCO 2 (25% and 41% compared to controls) starting at 7 days of exposure to hypoxia. At the cellular level, mitochondrial O 2 consumption in brain cortex increased after one day of hypoxia and then returned to control levels. A mild uncoupling was also observed in the cerebral mitochondria of mice. Contrastingly, no change was observed in rats. These results show that mice, are able to increase their aerobic metabolism during acclimatization to chronic hypoxia, while rats are not. Given that this phenotype is also present in other rodent species adapted to high altitude, our findings support hypothesis that mice, but not rats, are pre‐adapted to high altitude hypoxia due to early events in their phylogeographic history. Support or Funding Information This research is conducted with the funds granted by the Natural Sciences and Engineering Research Council of Canada. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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.
Inhibition of Protein Kinases AKT and ERK1/2 Reduce the Carotid Body Chemoreceptor Response to Hypoxia in Adult Rats
(Springer Nature, 2015) Pablo Iturri; Vincent Joseph; Gloria Rodrigo; Aïda Bairam; Jorge Soliz
Life-long consequences of postnatal normoxia exposure in rats raised at high altitude
(American Physiological Society, 2011) Delphine Lumbroso; A. Lemoine; Marcelino Gonzales; Gabriela Villalpando; Tommy Seaborn; Vincent Joseph
We tested the hypothesis that exposure of high-altitude (HA) rats to a period of postnatal normoxia has long-term consequences on the ventilatory and hematological acclimatization in adults. Male and female HA rats (3,600 m, Po 2 ≃ 100 Torr; La Paz, Bolivia) were exposed to normal room air [HA control (HACont)] or enriched oxygen (32% O 2 ; Po 2 ≃ 160 Torr) from 1 day before to 15 days after birth [HA postnatal normoxia (HApNorm)]. Hematocrit and hemoglobin values were assessed at 2, 12, and 32 wk of age. Cardiac and lung morphology were assessed at 12 wk by measuring right ventricular hypertrophy (pulmonary hypertension index) and lung air space-to-tissue ratio (indicative of alveolarization). Respiratory parameters under baseline conditions and in response to 32% O 2 for 10 min (relieving the ambient hypoxic stimulus) were measured by whole body plethysmography at 12 wk. Finally, we performed a survival analysis up to 600 days of age. Compared with HACont, HApNorm rats had reduced hematocrit and hemoglobin levels at all ages (both sexes); reduced right ventricular hypertrophy (both sexes); lower air space-to-tissue ratio in the lungs (males only); reduced CO 2 production rate, but higher oxygen uptake (males only); and similar respiratory frequency, tidal volume, and minute ventilation. When breathing 32% O 2 , HApNorm male rats had a stronger decrease of minute ventilation than HACont. HApNorm rats had a marked tendency toward longer survival throughout the study. We conclude that exposure to ambient hypoxia during postnatal development in HA rats has deleterious consequences on acclimatization to hypoxia as adults.
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 >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 >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.
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
The central chemosensitivity is not altered by cerebral erythropoietin
(Elsevier BV, 2015) Orlane Ballot; Sofien Laouafa; Elizabeth Elliot‐Portal; Rose Tam; Nicolas Voituron; Vincent Joseph; Jorge Soliz
Tracking the ancestral functions of erythropoietin: neuroprotection & mitochondria
(Wiley, 2020) Jorge Soliz; Karen Losantos-Ramos; Renato Suarez; Christian Arias‐Reyes; Sofien Laouafa; Daniela Furrer; Vincent Joseph
It has long been thought that erythropoietin (Epo) is exclusively involved in erythropoiesis, allowing erythroid progenitor cells to survive and mature through their antiapoptotic action. We now know that Epo in mammals has also other functions in the brain, playing key roles in the development, maintenance, protection, and repair of the nervous system. However, the recombinant human Epo (rhEpo) has neuroprotective effects in orthoptera insects (such as grasshoppers), and this effect appears to be mediated by the cytokine receptor‐like factor 3 (CRLF3), raising interesting questions about the evolutionary origin of the Epo signaling pathway and its role in invertebrate species. Taking into account that: 1) Epo in mammals modulates the mitochondrial oxidative phosphorylation and the production of reactive oxygen species (ROS) in several tissues, including the brain; and 2) that insects appeared during a geological period (Cambrian explosion) in which the atmospheric O 2 was increasing and required the implementation of antioxidant systems at the cellular level; here we tested the hypothesis that activation of the “Epo‐like” system in the brain domestic crickets ( Acheta domesticus ) exposed to 6 % of hypoxia during 5 days , modulates mitochondrial functions for preventing against oxidative damages. To do so, we used our oxygraph‐2K system (OROBOROS) that measures the mitochondrial bioenergetics in saponin‐permeabilized tissue of 2 mg weight. Our preliminary results showed that rhEpo increased the survival of domestic crickets exposed to hypoxia by 20%. We showed also that, in normoxic animals, rhEpo increased the mitochondrial O2 consumption rate (OCR), but in hypoxic animals, rhEPO limited the increase of mitochondrial OCR. In parallel, rhEpo significantly decreased the production of ROS in hypoxia. These preliminary results suggest that rhEpo significantly improves cricket’s survival under hypoxia, by promoting a robust antioxidant effect through mitochondria. Our data also suggest that a neuroprotective “Epo‐like” endogenous molecule evolved during the “Cambrian explosion” from a urbilaterian (common to vertebrates and invertebrates) ancestor. Support or Funding Information Natural Sciences and Engineering Research Council of Canada