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Respir Physiol Neurobiol. 2019 Sep;267:12-19. doi: 10.1016/j.resp.2019.05.012. Epub 2019 May 30.

Developmental expression patterns of erythropoietin and its receptor in mouse brainstem respiratory regions.

Author information

1
Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
2
Institut universitaire de cardiologie et de pneumologie de Québec, Centre Hospitalier Universitaire de Québec (CHUQ), Faculty of Medicine, Université Laval, Québec, QC, Canada.
3
Institut universitaire de cardiologie et de pneumologie de Québec, Centre Hospitalier Universitaire de Québec (CHUQ), Faculty of Medicine, Université Laval, Québec, QC, Canada; Instituto de Biología Molecular y Biotecnología, Facultad de Ciencias Puras y Naturales, Universidad Mayor de San Andrés, La Paz, Bolivia.
4
Institute of Veterinary Physiology and Zurich Center of Integrative Human Physiology (ZIHP), Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.
5
Institut universitaire de cardiologie et de pneumologie de Québec, Centre Hospitalier Universitaire de Québec (CHUQ), Faculty of Medicine, Université Laval, Québec, QC, Canada; Instituto de Biología Molecular y Biotecnología, Facultad de Ciencias Puras y Naturales, Universidad Mayor de San Andrés, La Paz, Bolivia. Electronic address: jorge.soliz@crchuq.ulaval.ca.

Abstract

Erythropoietin (EPO) is a hypoxia-inducible hormone, classically known to enhance red blood cell production upon binding its receptor (EPOR) present on the surface of the erythroid progenitor cells. EPO and its receptor are also expressed in the central nervous system (CNS), exerting several non-hematopoietic actions. EPO also plays an important role in the control of breathing. In this review, we summarize the known physiological actions of EPO in the neural control of ventilation during postnatal development and at adulthood in rodents under normoxic and hypoxic conditions. Furthermore, we present the developmental expression patterns of EPO and EPORs in the brainstem, and with the use of in situ hybridization (ISH) and immunofluorescence techniques we provide original data showing that EPOR is abundantly present in specific brainstem nuclei associated with central chemosensitivity and control of ventilation in the ventrolateral medulla, mainly on somatostatin negative cells. Thus, we conclude that EPO signaling may act through glutamatergic neuron populations that are the primary source of rhythmic inspiratory excitatory drive. This work underlies the importance of EPO signaling in the central control of ventilation across development and adulthood and provides new insights on the expression of EPOR at the cellular level.

KEYWORDS:

Brain development; Catecholaminergic nuclei; Cytokines; Pre-bötzinger complex

PMID:
31154093
DOI:
10.1016/j.resp.2019.05.012

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