Effet d'une surexpression d'érythropoïétine cérébrale sur la régulation et la mise en place post-natales du système nerveux de contrôle respiratoire chez la souris
|Authors:||Caravagna, Céline Michelle|
|Abstract:||Erythropoietin (Epo) is a cytokin expressed in the central nervous system (CNS). At adulthood, Epo acts as a respiratory modulator which enhances hypoxia ventilatory response (HVR) in both human and mouse. Respiratory disorders in newborns are common, as such finding an adapted treatment is of first interest. I hypothesized that chronic Epo stimulation on the CNS of newborns is helpfull to the central respiratory command to develop and respond to hypoxia. To test this hypothesis, I recorded breathing of transgenic mice overexpressing Epo in the CNS only (Tg21). HVR, which normally sets up during post-natal development, appears earlier in Tg21 mice, but is not higher as observed at adulthood in Tg21 mice. We quantified Epo and EpoR expression in Tg21 brainstems. EpoR expression decreases during post-natal development, while Epo overexpression is enhanced. These results could explain the late apparition of HVR enhancement. Then, I studied the underlying mecanisms. By electrophysiological recordings, I showed that usual rhythm depression due to hypoxia is not present in Tg21 brainstems-spinal cord preparations. In vitro, Tg21 brainstem is able to maintain the respiratory rhythm during hypoxia. Moreover, burst pattern from Tg21 mice on the first day of post-natal life looks like the burst pattern at three living days, which suggests an earlier maturation of the central respiratory system. However, this observation needs to be confirmed. In other roles (e.g. erythropoietic and neuroprotector) Epo recruits different pathways, mostly MEK-ERK and PI3K-Akt pathways. I hypothesized that these pathways are also involved in Epo effect on the central respiratory command. Thank to specific inhibitors, I highlighted that one of these pathways is not sufficient to support Epo role on newborn breathing, suggestiong a compensatory mechanism.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||23 April 2018|
|Collection:||Thèses et mémoires|
All documents in CorpusUL are protected by Copyright Act of Canada.