| First Author | Barioni NO | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 12 | Pages | eabm1444 |
| PubMed ID | 35333571 | Mgi Jnum | J:325580 |
| Mgi Id | MGI:7260968 | Doi | 10.1126/sciadv.abm1444 |
| Citation | Barioni NO, et al. (2022) Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia. Sci Adv 8(12):eabm1444 |
| abstractText | As blood oxygenation decreases (hypoxemia), mammals mount cardiorespiratory responses, increasing oxygen to vital organs. The carotid bodies are the primary oxygen chemoreceptors for breathing, but sympathetic-mediated cardiovascular responses to hypoxia persist in their absence, suggesting additional high-fidelity oxygen sensors. We show that spinal thoracic sympathetic preganglionic neurons are excited by hypoxia and silenced by hyperoxia, independent of surrounding astrocytes. These spinal oxygen sensors (SOS) enhance sympatho-respiratory activity induced by CNS asphyxia-like stimuli, suggesting they bestow a life-or-death advantage. Our data suggest the SOS use a mechanism involving neuronal nitric oxide synthase 1 (NOS1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). We propose NOS1 serves as an oxygen-dependent sink for NADPH in hyperoxia. In hypoxia, NADPH catabolism by NOS1 decreases, increasing availability of NADPH to NOX and launching reactive oxygen species-dependent processes, including transient receptor potential channel activation. Equipped with this mechanism, SOS are likely broadly important for physiological regulation in chronic disease, spinal cord injury, and cardiorespiratory crisis. |
