Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia

被引：17

作者：

Barioni, Nicole O. ^{[1
,2
]}

Derakhshan, Fatemeh ^{[1
,2
]}

Lopes, Luana Tenorio ^{[1
,2
]}

Onimaru, Hiroshi ^{[3
]}

Roy, Arijit ^{[1
,2
]}

McDonald, Fiona ^{[1
,2
]}

Scheibli, Erika ^{[1
,2
]}

Baghdadwala, Mufaddal, I ^{[1
,2
]}

Heidari, Negar ^{[1
,2
]}

Bharadia, Manisha ^{[1
,2
]}

Ikeda, Keiko ^{[4
]}

Yazawa, Itaru ^{[5
]}

Okada, Yasumasa ^{[4
]}

Harris, Michael B. ^{[6
]}

Dutschmann, Mathias ^{[7
]}

Wilson, Richard J. A. ^{[1
,2
]}

机构：

[1] Univ Calgary, Dept Physiol & Pharmacol, Hotchkiss Brain Inst, Cumming Sch Med, Calgary, AB, Canada

[2] Univ Calgary, Alberta Childrens Hosp Res Inst, Cumming Sch Med, Calgary, AB, Canada

[3] Showa Univ, Dept Physiol, Sch Med, Tokyo, Japan

[4] Murayama Med Ctr, Div Internal Med, Tokyo, Japan

[5] Hoshi Univ, Global Res Ctr Innovat Life Sci, Peptide Drug Innovat, Sch Pharm & Pharmaceut Sci, Tokyo 1428501, Japan

[6] Calif State Univ Long Beach, Dept Biol Sci, Long Beach, CA 90840 USA

[7] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic 3052, Australia

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 12期

基金：

美国国家卫生研究院; 加拿大健康研究院; 英国医学研究理事会;

关键词：

NITRIC-OXIDE SYNTHASE; SYMPATHETIC PREGANGLIONIC NEURONS; INTERMITTENT HYPOXIA; AFFERENT ACTIVITY; TRP CHANNELS; BRAIN-STEM; IN-VIVO; CALCIUM; RECEPTOR; CHEMORECEPTORS;

D O I：

10.1126/sciadv.abm1444

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：21

共 84 条

[1] THE EFFECTS OF BLOOD FLOW AND ANOXIA ON SPINAL CARDIOVASCULAR CENTERS [J].