Oxygen sensing in the brain--invited article.

Area of Science:

• Neuroscience
• Respiratory Physiology
• Cellular Biology

Background:

• Carotid body chemoreceptors are crucial for hypoxic ventilatory response (HVR) and acclimatization to hypoxia (VAH).
• Emerging evidence highlights the brain's role in O(2)-sensing for these respiratory adaptations.
• Central O(2)-sensing occurs in multiple brain regions, including the rostral ventrolateral medulla and hypothalamus.

Purpose of the Study:

• To investigate the role of central O(2)-sensing in acute HVR and chronic VAH.
• To elucidate the cellular and molecular mechanisms underlying central O(2)-sensing.
• To understand how brain plasticity contributes to ventilatory control under hypoxic conditions.

Main Methods:

• Review of existing literature on central O(2)-sensing and respiratory control.
• Analysis of studies investigating brainstem and hypothalamic O(2)-sensing pathways.
• Examination of molecular mechanisms, including ion channels, heme oxygenase-2, and gene expression.

Main Results:

• Central O(2)-sensing in specific brain regions contributes significantly to acute HVR.
• Chronic hypoxia induces brain plasticity involved in VAH, representing a distinct temporal domain of central O(2)-sensing.
• Mechanisms of acute central O(2)-sensing may involve O(2)-sensitive ion channels and heme oxygenase-2, differing from carotid body mechanisms.
• O(2)-sensitive gene expression in the brain, regulated by hypoxia-inducible factor-1 (HIF-1), plays a role in VAH.

Conclusions:

• The brain is a critical site for O(2)-sensing, complementing peripheral carotid body function in respiratory control.
• Central O(2)-sensing exhibits distinct temporal dynamics, with acute responses and chronic plasticity contributing to adaptation to hypoxia.
• Understanding these central mechanisms, including gene expression pathways like HIF-1, is vital for comprehending ventilatory control during hypoxia.