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Identification of a new population of TrkC+ sensory neurons that regulates blood pressure

Morelli, Chiara

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Abstract

Blood pressure is one of the vital signs and its regulation is crucial for survival. Several mechanisms contribute to maintain it in a physiological range: renin-angiotensin-aldosterone system, the autonomous nervous system and specialized baroreceptors neurons. In this study, we demonstrate the existence of a new population of sensory neurons marked by TrkC and TH that innervate blood vessels and are important in the control of blood pressure, blood flow and heart rate. Using an inducible Cre line driven from the TrkC locus, we show that TrkC is expressed in 30% of DRG neurons and that a fourth of these neurons are TH+ and project to blood vessels. Activation of TrkC+ TH+ neurons leads to high blood pressure, decreased blood flow and increased heart rate variability. Loss of function experiments revealed that TrkC+ TH+ sensory neurons are crucial for life. Ablation of TrkC+ neurons results in low blood pressure, alteration of blood flow and increased heart rate variability. All these cardiovascular alterations lead ablate mice to death within 48 hours. We also demonstrate that TrkC+ neurons do not act directly on blood vessels, but they exert their functions through a circuit with the sympathetic nervous system. We thus identified a new population of sensory neurons involved in the regulation of blood pressure, blood flow and heart rate and we hope that this can lead to the development of new therapeutic strategies in the near future.

Document type: Dissertation
Supervisor: Asari, Dr. Hiroki
Place of Publication: Heidelberg
Date of thesis defense: 25 June 2019
Date Deposited: 22 Nov 2019 08:23
Date: 2020
Faculties / Institutes: The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences
DDC-classification: 500 Natural sciences and mathematics
Controlled Keywords: PNS, blood pressure
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