BACKGROUND: Hypoxia is perceived as pivotal physiological driving force, allowing cells in brain and elsewhere to acclimate to lowered oxygen (O2) and abridged metabolism. The adaptation-mediating transcription program is induced by inspiratory hypoxia and/or 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 are hypoxia-inducible factors (HIF) and associated prolyl-hydroxylases. HIF are transcription factors, stabilized by low O2 accessibility, and control expression of a multitude of genes, among them the potent procognitive growth factor erythropoietin (EPO). 
OBJECTIVES: Considering the far-reaching biological response to hypoxia which includes the activation of the cerebral EPO system, we initiated a first translational project, combining mild to moderate inspiratory with functional hypoxia. We had identified this combination earlier to benefit motor-cognitive attainment in mice. 
METHODS: A total of 20 subjects were included, 13 healthy individuals and 7 patients with depression, schizophrenia, and/or autism spectrum disorder. 
RESULTS: We show that motor-cognitive training under inspiratory hypoxia (12% O2) for 3.5 hours daily over 3 weeks is optimally tolerated. We present first signals of beneficial effects on general well-being, cognitive performance, physical fitness and psychopathology. EPO in serum increased under hypoxia. Flow cytometry of blood confirmed that mononuclear cell composition in blood of adults was not affected. 
CONCLUSIONS: Motor-cognitive training under inspiratory hypoxia is well tolerated by healthy individuals as well as by patients with depression, schizophrenia, and/or autism spectrum disorder. EPO is likely a pivotal mediator of the observed beneficial effects. To obtain reliable information regarding the ′add-on′ value of inspiratory on top of functional hypoxia, however, a single-blind study - with versus without inspiratory hypoxia - is required.

Lecturer:
Prof. Dr. med. Dr. med. vet. Hannelore Ehrenreich

Contact:
Agnes Janßen (ajanssen@neuro.uni-bremen.de)