Endogenous brain erythropoietin is a potent sex-specific respiratory stimulant in adult and newborn mice

Journal of Applied Physiology
Orlane BallotJorge Soliz

Abstract

We tested the hypothesis that endogenous brain Epo is a respiratory stimulant. Adult (3 mo) and newborn (10 days) male and female mice received an intracisternal (cisterna magna) injection of soluble Epo receptor (sEpoR; competes with EpoR to bind Epo; 50 μg/ml) or vehicle (0.1% BSA in PBS). Twenty-four hours after injection, we used whole body plethysmography to record minute ventilation (V̇e) tidal volume (VT), respiratory frequency (fR), O2 consumption (V̇o2), and CO2 production (V̇co2) under normoxia and progressive exposure to hypoxia (12-10-6% O2; 10 min each). In adult male and female mice sEpoR decreased normoxic V̇e (-25%), due to a decrease of VT in males and fR in females. Moreover, sEpoR injection decreased the ventilatory response to 12% O2, assessed as V̇e/V̇o2 or V̇e/V̇co2, in male but not in female mice. In newborn male and female mice sEpoR decreased V̇e (-37% in males, -59% in females) and VT (-38% in males, -47% in females) in normoxia and fR in females. During hypoxia, sEpoR decreased V̇e/V̇o2 and V̇e/V̇co2 in mice of both sexes. Upon extreme hypoxia (6% O2), the newborn mice treated with sEpoR showed respiratory depression, signs of asphyxia (gasping) and a high mortality rate in males and females. We concl...Continue Reading

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Citations

Oct 17, 2015·Neuroscience Letters·Orlane BallotJorge Soliz
Jun 13, 2015·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Céline CaravagnaJorge Soliz
Mar 12, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yuanyuan ZhangConstance Tom Noguchi
Nov 3, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Sofien LaouafaJorge Soliz

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