Erythropoietin and respiratory control at adulthood and during early postnatal life

Abstract

Erythropoietin (Epo) was originally discovered as a cytokine able to increase the production of red blood cells upon conditions of reduced oxygen availability. Now we know that Epo does far more than "only" augmenting the number of erythrocytes. Since the demonstration that Epo (and its receptor) is expressed in the mammalian brain, several elegant experiments were performed to reveal the function of this molecule in the neuronal tissue. Accordingly to its anti-apoptotic, neurotrophic and proliferative effects in the bone marrow, it was suitably suggested that upon pathological conditions Epo exerts neuroprotective functions (i.e. reducing the infarct volume of stroke, thus allowing better and faster recovery). We considered however, that Epo in brain might also exert a physiological function. Indeed, we found that Epo is an important modulator of the respiratory control system. By using adult mice we showed that Epo increases the hypoxic ventilatory response by interacting with both the central respiratory network (brainstem) as well as the main peripheral sensory organs detecting systemic hypoxia, the carotid bodies. More recently, our research turned to examine the exciting hypothesis that Epo is also implicated in the regulation of the neuronal control of ventilation during the postnatal development. The objective of this review is to summarize the role and mode of action of Epo on respiratory control in adult mammals and highlight the potential pathways by which this cytokine achieve this function. Additionally, we review recent evidences showing that Epo play a crucial role in setting the respiratory motor output (measured on the isolated brainstem spinal cord preparation, en bloc technique) during the early postnatal life.