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Brain‐derived erythropoietin modulates the hypercapnic ventilatory response during early postnatal life
Author(s) -
Soliz Jorge
Publication year - 2013
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.27.1_supplement.1137.26
Subject(s) - hypoxic ventilatory response , normocapnia , erythropoietin , hypercapnia , pons , medulla oblongata , ventilation (architecture) , medicine , respiratory system , brainstem , endocrinology , neuroscience , biology , central nervous system , mechanical engineering , engineering
Apart from neuroprotective roles against stroke, erythropoietin (Epo) in brain (i.e. Epo synthesized in neurons and astrocytes) modulates the ventilatory response to hypoxia of mice and human. This effect was attributed to the presence of Epo receptors (EpoR) in neurons involved in respiratory rhythmogenesis (e.g., the pre‐Bötzinger complex), sensory integration (nucleus tractus solitarius) and in catecholaminergic neural populations (A6 and A5 in the pons; A2/C2 and A1/C1 in the medulla oblongata). Apart from hypoxia however, central and peripheral chemoreceptors regulate the ventilatory response to carbon dioxide. In this study we used C57Bl6 mice at postnatal ages 10, 15 and 21 days, to test the hypothesis that brain‐derived Epo impacts the hypercapnic ventilatory response during the postnatal development. Animals were injected (i.p.) with Epo (500 U/mouse) 24h before experimentation. Subsequently, baseline ventilation (normocapnia; 5 min), hypercapnic ventilatory response (5% CO 2 , 21% O 2 in N 2 ; 5 min), and recovery (normocapnia; 5 min) were evaluated by whole body plethysmography. Our preliminary results show that Epo increases the hypercapnic ventilatory response at P10, has no effect at P15, and decreases the hypercapnic ventilatory response at P21. Furthermore, by using antibodies to paired‐like homeobox 2b (Phox2b), Epo and Epo receptor were localized to the retrotrapezoid nucleus (RTN) at postnatal day 10. These novel findings imply that Epo plays a key‐regulating role in the neural response to carbon dioxide in a period in which the central respiratory network undergoes full development and maturation.