Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress
Abstract Hypoxia is increasingly recognized as an important physiological driving force. A specific transcriptional program, induced by a decrease in oxygen (O2) availability, for example, inspiratory hypoxia at high altitude, allows cells to adapt to lower O2 and limited energy metabolism. This tra...
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Neuroprotection |
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| Online Access: | https://doi.org/10.1002/nep3.15 |
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| author | Hannelore Ehrenreich Max Gassmann Luise Poustka Martin Burtscher Peter Hammermann Anna‐Leena Sirén Klaus‐Armin Nave Kamilla Miskowiak |
| author_facet | Hannelore Ehrenreich Max Gassmann Luise Poustka Martin Burtscher Peter Hammermann Anna‐Leena Sirén Klaus‐Armin Nave Kamilla Miskowiak |
| author_sort | Hannelore Ehrenreich |
| collection | DOAJ |
| description | Abstract Hypoxia is increasingly recognized as an important physiological driving force. A specific transcriptional program, induced by a decrease in oxygen (O2) availability, for example, inspiratory hypoxia at high altitude, allows cells to adapt to lower O2 and limited energy metabolism. This transcriptional program is partly controlled by and partly independent of hypoxia‐inducible factors. Remarkably, this same transcriptional program is stimulated in the brain by extensive motor‐cognitive exercise, leading to a relative decrease in O2 supply, compared to the acutely augmented O2 requirement. We have coined the term “functional hypoxia” for this important demand‐responsive, relative reduction in O2 availability. Functional hypoxia seems to be critical for enduring adaptation to higher physiological challenge that includes substantial “brain hardware upgrade,” underlying advanced performance. Hypoxia‐induced erythropoietin expression in the brain likely plays a decisive role in these processes, which can be imitated by recombinant human erythropoietin treatment. This article review presents hints of how inspiratory O2 manipulations can potentially contribute to enhanced brain function. It thereby provides the ground for exploiting moderate inspiratory plus functional hypoxia to treat individuals with brain disease. Finally, it sketches a planned multistep pilot study in healthy volunteers and first patients, about to start, aiming at improved performance upon motor‐cognitive training under inspiratory hypoxia. |
| format | Article |
| id | doaj-art-18eb684a1f3e4f4f8a82ae2db81837d7 |
| institution | DOAJ |
| issn | 2770-7296 2770-730X |
| language | English |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neuroprotection |
| spelling | doaj-art-18eb684a1f3e4f4f8a82ae2db81837d72025-08-20T02:40:29ZengWileyNeuroprotection2770-72962770-730X2023-09-0111556510.1002/nep3.15Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progressHannelore Ehrenreich0Max Gassmann1Luise Poustka2Martin Burtscher3Peter Hammermann4Anna‐Leena Sirén5Klaus‐Armin Nave6Kamilla Miskowiak7Clinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences Göttingen GermanyInstitute of Veterinary Physiology and Zürich Center for Integrative Human Physiology University of Zürich Zürich SwitzerlandDepartment of Child and Adolescent Psychiatry and Psychotherapy University Medical Center Göttingen Göttingen GermanyFaculty of Sports Science University of Innsbruck Innsbruck AustriaHBL Investmentpartners GmbH München‐Frankfurt GermanyDepartments of Neurophysiology and Neurosurgery University of Würzburg Würzburg GermanyDepartment of Neurogenetics Max Planck Institute for Multidisciplinary Sciences Göttingen GermanyPsychiatric Centre Copenhagen University Hospital, Rigshospitalet Copenhagen DenmarkAbstract Hypoxia is increasingly recognized as an important physiological driving force. A specific transcriptional program, induced by a decrease in oxygen (O2) availability, for example, inspiratory hypoxia at high altitude, allows cells to adapt to lower O2 and limited energy metabolism. This transcriptional program is partly controlled by and partly independent of hypoxia‐inducible factors. Remarkably, this same transcriptional program is stimulated in the brain by extensive motor‐cognitive exercise, leading to a relative decrease in O2 supply, compared to the acutely augmented O2 requirement. We have coined the term “functional hypoxia” for this important demand‐responsive, relative reduction in O2 availability. Functional hypoxia seems to be critical for enduring adaptation to higher physiological challenge that includes substantial “brain hardware upgrade,” underlying advanced performance. Hypoxia‐induced erythropoietin expression in the brain likely plays a decisive role in these processes, which can be imitated by recombinant human erythropoietin treatment. This article review presents hints of how inspiratory O2 manipulations can potentially contribute to enhanced brain function. It thereby provides the ground for exploiting moderate inspiratory plus functional hypoxia to treat individuals with brain disease. Finally, it sketches a planned multistep pilot study in healthy volunteers and first patients, about to start, aiming at improved performance upon motor‐cognitive training under inspiratory hypoxia.https://doi.org/10.1002/nep3.15brain EPO circleerythropoietinfunctional hypoxiaHIFhuman pilot studyhyperoxia |
| spellingShingle | Hannelore Ehrenreich Max Gassmann Luise Poustka Martin Burtscher Peter Hammermann Anna‐Leena Sirén Klaus‐Armin Nave Kamilla Miskowiak Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress Neuroprotection brain EPO circle erythropoietin functional hypoxia HIF human pilot study hyperoxia |
| title | Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress |
| title_full | Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress |
| title_fullStr | Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress |
| title_full_unstemmed | Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress |
| title_short | Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress |
| title_sort | exploiting moderate hypoxia to benefit patients with brain disease molecular mechanisms and translational research in progress |
| topic | brain EPO circle erythropoietin functional hypoxia HIF human pilot study hyperoxia |
| url | https://doi.org/10.1002/nep3.15 |
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