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Erythropoietin and its antagonist regulate the hypoxic fictive breathing in newborn mice
Author(s) -
Soliz Jorge,
Khemiri Hanan,
Seaborn Tommy
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1089.1
Subject(s) - erythropoietin , brainstem , antagonist , hypoxia (environmental) , respiratory system , endogeny , medicine , receptor antagonist , respiration , receptor , hypoxic ventilatory response , endocrinology , anesthesia , pharmacology , chemistry , anatomy , oxygen , organic chemistry
Erythropoietin (Epo) in adult mouse interacts with the major brainstem centers associated with respiration to enhance the ventilatory response to acute and chronic conditions of physiological hypoxia (e.g. as occuring at high altitude). However, whether Epo is as well implicated in the regulation of breathing in newborns remains unknown. To answer this question en bloc brainstem‐spinal cord preparations were obtained from mice at postnatal day 4 (P4). After time‐ (30, 60 or 90 min) and dose‐dependent (0, 25 or 250 U) incubation with or without Epo, en bloc preparations were superfused with artificial cerebrospinal fluid (aCSF) bubbled with normoxic or hypoxic gas mixtures. Subsequently, the electrophysiological fictive breathing produced by axons at the C4 ventral root was recorded. Our results show that upon hypoxic conditions Epo stimulates the neural hypoxic respiratory activity and improves the post hypoxic recovery. In addition, proof‐of‐concept experiments showed that soluble Epo receptor (sEpoR), the endogenous antagonist of Epo, dramatically decreases the neural hypoxic respiratory activity. These results imply that Epo and its endogenous antagonist in P4 mice are implicated in the modulation and maintenance of respiratory motor output during hypoxic and post‐hypoxic challenges. As Epo is a highly promising protective therapeutic agent for several brain diseases, these results suggest that Epo applications may be also relevant for neuronal‐related respiratory disorders in term and preterm neonates.