Oxygen-sensing neurons in the central nervous system

Abstract

This mini-review summarizes the present knowledge regarding central oxygen-chemosensitive sites with special emphasis on their function in regulating changes in cardiovascular and respiratory responses. These oxygen-chemosensitive sites are distributed throughout the brain stem from the thalamus to the medulla and may form an oxygen-chemosensitive network. The ultimate effect on respiratory or sympathetic activity presumably depends on the specific neural projections from each of these brain stem oxygen-sensitive regions as well as on the developmental age of the animal. Little is known regarding the cellular mechanisms involved in the chemotransduction process of the central oxygen sensors. The limited information available suggests some conservation of mechanisms used by other oxygen-sensing systems, e.g., carotid body glomus cells and pulmonary vascular smooth muscle cells. However, major gaps exist in our understanding of the specific ion channels and oxygen sensors required for transducing central hypoxia by these central oxygen-sensitive neurons. Adaptation of these central oxygen-sensitive neurons during chronic or intermittent hypoxia likely contributes to responses in both physiological conditions (ascent to high altitude, hypoxic conditioning) and clinical conditions (heart failure, chronic obstructive pulmonary disease, obstructive sleep apnea syndrome, hypoventilation syndromes). This review underscores the lack of knowledge about central oxygen chemosensors and highlights real opportunities for future research.

Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep

“…The effect of hypoxia may be related to less central ventilatory drive (40) as result of medullary hypocapnia due to hypoxia-induced hyperventilation and increased cerebral blood flow. Thus hypoxia may enhance periodic breathing and apnea through a combination of its stimulating effect on the peripheral chemoreceptor and its suppressive effect on central respiratory drive (26,41) and via increased cerebral blood flow (12). In other words, even though peripheral chemoreceptor presence is necessary for the manifestation of a rapid-onset posthyperventilation apnea, additional central influences are required to produce periodic breathing.…”

Noradrenergic modulation of respiratory motor output during tadpole development: role of α-adrenoceptors

“…In mammals, many noradrenergic neurons are hypoxia sensitive and have been implicated in the ventilatory response to hypoxia (Neubauer and Sunderram, 2004;Roux et al, 2000;Soulier et al, 1997). In pre-metamorphic tadpoles, activation of noradrenergic neurons by hypoxia would tend to facilitate both lung and buccal ventilation.…”

Effects of Hyperoxia on Brain Tissue Oxygen Tension in Non-Sedated, Non- Anesthetized Arctic Ground Squirrels: An Animal Model of Hyperoxic Stress

“…Therefore, hyperoxic gas mixtures are routinely used for chemical denervation of peripheral O 2 receptors in in-vivo studies of respiratory control. The response mechanisms under hyperoxic inhalation conditions are commonly considered to be regulated by oxygen-chemosensitive neurons of the central nerve system, which are distributed throughout the brain stem from the thalamus to the medulla (Neubauer and Sunderram, 2004;Dean et al, 2003Dean et al, , 2004Mulkey et al, 2001). Therefore, the higher response level of P t O 2 during 100% O 2 inhalation in AGS compared to rat is accounted by the regulation mechanism controlled by oxygen-chemosensitive neurons of the central nerve system.…”