Environmental and behavioral regulation of HIF-mitochondria crosstalk

Introduction: The human brain is a highly oxygen-dependent organ. Low environmental oxygen availability (e.g., hypobaric hypoxia at altitude) is a major challenge to the brain and numerous endogenous cellular and systemic hypoxia responses therefore are in place to mitigate hypoxic stress. When the dose of the hypoxic stress surpasses the adaptive capabilities of the brain, cerebral forms of high-altitude illnesses can develop, the prevalence of which increases with the altitude. Hypoxia can also trigger psychotic symptoms. Despite that, the effects of altitude exposures on people with pre-existing mental disorders are surprisingly scarcely investigated. Methods: In this narrative review we summarize the literature on the brain’s responses to hypoxia and put them in the context of somatic high-altitude illnesses and mental consequences of altitude exposure from an interdisciplinary perspective. Results: We identify knowledge gaps with high clinical relevance related to the safety of altitude exposures, particularly for individuals with mental disorders. Conclusions: Taken together, research into the vulnerability of people with neuropsychiatric disorders and the risk of developing mental symptoms in different populations (diseased, healthy, athletes) at altitude is urgently needed to provide appropriate evidence-based counselling and treatment.

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Mechanisms underlying the health benefits of intermittent hypoxia conditioning

Burtscher,

Citherlet,

Camacho‐Cardenosa

et al. 2023

The Journal of Physiology

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Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non‐pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long‐term adaptation to maladaptation and the development of pathologies. Rather than discussing in detail the well‐characterized individual responses and adaptations to IH, we here aim to summarize and integrate hypoxia‐activated mechanisms into a holistic picture of the body's adaptive responses to hypoxia and specifically IH, and demonstrate how these mechanisms might be mobilized for their health benefits while minimizing the risks of hypoxia exposure. image

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Environmental and behavioral regulation of HIF-mitochondria crosstalk

Cited by 5 publications

References 200 publications

The interplay of NAD and hypoxic stress and its relevance for ageing

The interplay of NAD and hypoxic stress and its relevance for ageing

High altitude adaptation, common high-altitude disorders and the effects of high altitude on mental health

Mechanisms underlying the health benefits of intermittent hypoxia conditioning

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