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Acute and chronic elevation of erythropoietin in the brain improves exercise performance in mice without inducing erythropoiesis


Schuler, Beat; Vogel, Johannes; Grenacher, Beat; Jacobs, Robert A; Arras, Margarete; Gassmann, Max (2012). Acute and chronic elevation of erythropoietin in the brain improves exercise performance in mice without inducing erythropoiesis. FASEB Journal, 26(9):3884-3890.

Abstract

Application of recombinant human erythropoietin (rhEpo) improves exercise capacity by stimulating red blood cell production that, in turn, enhances oxygen delivery and utilization. Apart from this, when applied at high doses, rhEpo crosses the blood-brain barrier, triggering protective neuronal effects. Here we show a fundamental new role by which the presence of Epo in the brain augments exercise performance without altering red blood cell production. Two different animal models, the transgenic mouse line Tg21, which constitutively overexpresses human Epo exclusively in the brain without affecting erythropoiesis, and wild-type mice treated with a single high dose of rhEpo, demonstrate an unexpected improvement in maximal exercise performance independent of changes in total hemoglobin mass, as well as in whole blood volume and cardiovascular parameters. This novel finding builds a more complete understanding regarding the central effects of endogenously produced and exogenously applied Epo on exercise performance.-Schuler, B., Vogel, J., Grenacher, B., Jacobs, R. A., Arras, M., Gassmann, M. Acute and chronic elevation of erythropoietin in the brain improves exercise performance in mice without inducing erythropoiesis.

Abstract

Application of recombinant human erythropoietin (rhEpo) improves exercise capacity by stimulating red blood cell production that, in turn, enhances oxygen delivery and utilization. Apart from this, when applied at high doses, rhEpo crosses the blood-brain barrier, triggering protective neuronal effects. Here we show a fundamental new role by which the presence of Epo in the brain augments exercise performance without altering red blood cell production. Two different animal models, the transgenic mouse line Tg21, which constitutively overexpresses human Epo exclusively in the brain without affecting erythropoiesis, and wild-type mice treated with a single high dose of rhEpo, demonstrate an unexpected improvement in maximal exercise performance independent of changes in total hemoglobin mass, as well as in whole blood volume and cardiovascular parameters. This novel finding builds a more complete understanding regarding the central effects of endogenously produced and exogenously applied Epo on exercise performance.-Schuler, B., Vogel, J., Grenacher, B., Jacobs, R. A., Arras, M., Gassmann, M. Acute and chronic elevation of erythropoietin in the brain improves exercise performance in mice without inducing erythropoiesis.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:06 Jul 2012 08:24
Last Modified:07 Dec 2017 14:24
Publisher:Federation of American Societies for Experimental Biology
ISSN:0892-6638
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1096/fj.11-191197
PubMed ID:22683849

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