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

• Published in: Respiratory physiology & neurobiology Vol. 267; pp. 12 - 19
• Main Authors: Schneider Gasser, Edith M., Elliot-Portal, Elizabeth, Arias-Reyes, Christian, Losantos-Ramos, Karen, Khalid, Kasifa, Ogunshola, Omolara, Soliz, Jorge
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2019
• Subjects: Animals; Animals, Newborn; Brain development; Brain Stem - growth & development; Brain Stem - metabolism; Catecholaminergic nuclei; Cytokines; Erythropoietin - biosynthesis; Erythropoietin - genetics; Gene Expression Regulation, Developmental; Humans; Mice; Pre-bötzinger complex; Pulmonary Ventilation - physiology; Receptors, Erythropoietin - biosynthesis; Receptors, Erythropoietin - genetics; Respiratory Mechanics - physiology; Pre-bötzinger complex; Cytokines; Catecholaminergic nuclei; Brain development
• ISSN: 1569-9048; 1878-1519
• DOI: 10.1016/j.resp.2019.05.012

•Epo in the brainstem is a potent regulator of the normoxic and hypoxic ventilation.•Epo receptors (EPOR) do not colocalize with Pre-Bötzinger complex-somatostatine positive cells.•Epo-mediated breathing regulation may act through glutamatergic cell populations in the brainstem. 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.