Tolerability and first hints for potential efficacy of motor‐cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint

Abstract Hypoxia is more and more perceived as pivotal physiological driving force, allowing cells in the brain and elsewhere to acclimate to lowered oxygen (O2), and abridged metabolism. The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor‐cognitive task...

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Main Authors: Svea‐Solveig Mennen, Maren Franta, Martin Begemann, Justus B. H. Wilke, Roman Schröder, Umer Javed Butt, Jonathan‐Alexis Cortés‐Silva, Umut Çakır, Marie Güra, Markus deMarées, Vinicius Daguano Gastaldi, Johannes Burtscher, Julie Schanz, Matthias Bohn, Martin Burtscher, Andreas Fischer, Luise Poustka, Peter Hammermann, Markus Stadler, Fred Lühder, Manvendra Singh, Klaus‐Armin Nave, Kamilla Woznica Miskowiak, Hannelore Ehrenreich
Format: Article
Language:English
Published: Wiley 2024-09-01
Series:Neuroprotection
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Online Access:https://doi.org/10.1002/nep3.47
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author Svea‐Solveig Mennen
Maren Franta
Martin Begemann
Justus B. H. Wilke
Roman Schröder
Umer Javed Butt
Jonathan‐Alexis Cortés‐Silva
Umut Çakır
Marie Güra
Markus deMarées
Vinicius Daguano Gastaldi
Johannes Burtscher
Julie Schanz
Matthias Bohn
Martin Burtscher
Andreas Fischer
Luise Poustka
Peter Hammermann
Markus Stadler
Fred Lühder
Manvendra Singh
Klaus‐Armin Nave
Kamilla Woznica Miskowiak
Hannelore Ehrenreich
author_facet Svea‐Solveig Mennen
Maren Franta
Martin Begemann
Justus B. H. Wilke
Roman Schröder
Umer Javed Butt
Jonathan‐Alexis Cortés‐Silva
Umut Çakır
Marie Güra
Markus deMarées
Vinicius Daguano Gastaldi
Johannes Burtscher
Julie Schanz
Matthias Bohn
Martin Burtscher
Andreas Fischer
Luise Poustka
Peter Hammermann
Markus Stadler
Fred Lühder
Manvendra Singh
Klaus‐Armin Nave
Kamilla Woznica Miskowiak
Hannelore Ehrenreich
author_sort Svea‐Solveig Mennen
collection DOAJ
description Abstract Hypoxia is more and more perceived as pivotal physiological driving force, allowing cells in the brain and elsewhere to acclimate to lowered oxygen (O2), and abridged metabolism. The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor‐cognitive tasks, provoking a relative decrease in O2 in relation to the acutely augmented requirement. We termed this fundamental, demand‐dependent drop in O2 availability “functional hypoxia.” Major players in the hypoxia response are hypoxia‐inducible factors (HIFs) and associated prolyl‐hydroxylases. HIFs are transcription factors, stabilized by low O2 accessibility, and control expression of a multitude of genes. Changes in oxygen, however, can also be sensed via other pathways, among them the thiol‐oxidase (2‐aminoethanethiol) dioxygenase. Considering the far‐reaching biological response to hypoxia, hitherto mostly observed in rodents, we initiated a translational project, combining mild to moderate inspiratory with functional hypoxia. We had identified this combination earlier to benefit motor‐cognitive attainment in mice. A total of 20 subjects were included: 13 healthy individuals and 7 patients with depression and/or autism spectrum disorder. Here, we show that motor‐cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is optimally tolerated. We present first signals of beneficial effects on general well‐being, cognitive performance, physical fitness and psychopathology. Erythropoietin in serum increases under hypoxia and flow cytometry analysis of blood reveals several immune cell types to be mildly modulated by hypoxia. To obtain reliable information regarding the “add‐on” value of inspiratory on top of functional hypoxia, induced by motor‐cognitive training, a single‐blind study—with versus without inspiratory hypoxia—is essential and outlined here.
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spelling doaj-art-7cb64752cbf64c18bd12c8a04c4432da2025-08-20T03:27:47ZengWileyNeuroprotection2770-72962770-730X2024-09-012322824210.1002/nep3.47Tolerability and first hints for potential efficacy of motor‐cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpointSvea‐Solveig Mennen0Maren Franta1Martin Begemann2Justus B. H. Wilke3Roman Schröder4Umer Javed Butt5Jonathan‐Alexis Cortés‐Silva6Umut Çakır7Marie Güra8Markus deMarées9Vinicius Daguano Gastaldi10Johannes Burtscher11Julie Schanz12Matthias Bohn13Martin Burtscher14Andreas Fischer15Luise Poustka16Peter Hammermann17Markus Stadler18Fred Lühder19Manvendra Singh20Klaus‐Armin Nave21Kamilla Woznica Miskowiak22Hannelore Ehrenreich23Clinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyDepartment of Sports Medicine Ruhr University Bochum GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyInstitute of Sports Science University of Lausanne Lausanne SwitzerlandDepartment of Clinical Chemistry and Interdisciplinary UMG Laboratory University Medical Center Göttingen Göttingen GermanyClinical Pharmacy Georg‐August‐University Göttingen GermanyFaculty of Sports Science University of Innsbruck Innsbruck AustriaDepartment of Clinical Chemistry and Interdisciplinary UMG Laboratory University Medical Center Göttingen Göttingen GermanyDepartment of Child and Adolescent Psychiatry & Psychotherapy, Center for Psychosocial Medicine University Hospital Heidelberg Heidelberg GermanyHBL Investmentpartners GmbH München‐Frankfurt GermanyDatico Sport & Health GmbH Burghausen GermanyInstitute for Neuroimmunology and Multiple Sclerosis Research University Medical Center Göttingen Göttingen GermanyClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyDepartment of Neurogenetics Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyFrederiksberg Hospital and Department of Psychology, Neurocognition and Emotion in Affective Disorders (NEAD) Centre, Copenhagen Affective Disorder Research Centre, Psychiatric Centre Copenhagen University of Copenhagen Copenhagen DenmarkClinical Neuroscience Max Planck Institute for Multidisciplinary Sciences City Campus Göttingen GermanyAbstract Hypoxia is more and more perceived as pivotal physiological driving force, allowing cells in the brain and elsewhere to acclimate to lowered oxygen (O2), and abridged metabolism. The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor‐cognitive tasks, provoking a relative decrease in O2 in relation to the acutely augmented requirement. We termed this fundamental, demand‐dependent drop in O2 availability “functional hypoxia.” Major players in the hypoxia response are hypoxia‐inducible factors (HIFs) and associated prolyl‐hydroxylases. HIFs are transcription factors, stabilized by low O2 accessibility, and control expression of a multitude of genes. Changes in oxygen, however, can also be sensed via other pathways, among them the thiol‐oxidase (2‐aminoethanethiol) dioxygenase. Considering the far‐reaching biological response to hypoxia, hitherto mostly observed in rodents, we initiated a translational project, combining mild to moderate inspiratory with functional hypoxia. We had identified this combination earlier to benefit motor‐cognitive attainment in mice. A total of 20 subjects were included: 13 healthy individuals and 7 patients with depression and/or autism spectrum disorder. Here, we show that motor‐cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is optimally tolerated. We present first signals of beneficial effects on general well‐being, cognitive performance, physical fitness and psychopathology. Erythropoietin in serum increases under hypoxia and flow cytometry analysis of blood reveals several immune cell types to be mildly modulated by hypoxia. To obtain reliable information regarding the “add‐on” value of inspiratory on top of functional hypoxia, induced by motor‐cognitive training, a single‐blind study—with versus without inspiratory hypoxia—is essential and outlined here.https://doi.org/10.1002/nep3.47braincognitionerythropoietinfunctional hypoxiahigh‐parameter flow cytometryimmune cells
spellingShingle Svea‐Solveig Mennen
Maren Franta
Martin Begemann
Justus B. H. Wilke
Roman Schröder
Umer Javed Butt
Jonathan‐Alexis Cortés‐Silva
Umut Çakır
Marie Güra
Markus deMarées
Vinicius Daguano Gastaldi
Johannes Burtscher
Julie Schanz
Matthias Bohn
Martin Burtscher
Andreas Fischer
Luise Poustka
Peter Hammermann
Markus Stadler
Fred Lühder
Manvendra Singh
Klaus‐Armin Nave
Kamilla Woznica Miskowiak
Hannelore Ehrenreich
Tolerability and first hints for potential efficacy of motor‐cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint
Neuroprotection
brain
cognition
erythropoietin
functional hypoxia
high‐parameter flow cytometry
immune cells
title Tolerability and first hints for potential efficacy of motor‐cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint
title_full Tolerability and first hints for potential efficacy of motor‐cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint
title_fullStr Tolerability and first hints for potential efficacy of motor‐cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint
title_full_unstemmed Tolerability and first hints for potential efficacy of motor‐cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint
title_short Tolerability and first hints for potential efficacy of motor‐cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint
title_sort tolerability and first hints for potential efficacy of motor cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders a translational viewpoint
topic brain
cognition
erythropoietin
functional hypoxia
high‐parameter flow cytometry
immune cells
url https://doi.org/10.1002/nep3.47
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