Themes: Biology, medicine, health
Thesis location: Experimental Radiotoxicology and Radiobiology Laboratory (LRTOX) - Fontenay-aux-Roses (92)
Start: October 2021
Knowledges in Physiology, cardiovascular biology
Age limit: 26 years old unless otherwise stated.
Ischemic heart disease, rhythm problems and heart failure are the main cardiac pathologies developed several years after cardiac exposure to moderate and high doses. These cardiac pathologies result mainly from lesions such as radiation-induced fibrosis, chronic inflammation, cardiac remodeling with cellular and molecular alteration. However, very few experimental studies have been conducted on the development of these pathologies after exposure to low doses of ionizing radiation (<300mGy). In the case of cardiac pathologies such as rhythm disorders, several studies demonstrated a link between the sympathetic nervous system (SNS) and the heart. Indeed, sympathetic overactivation is crucial in the development of remodeling and cardiac dysfunction. It has been suggested that cardiac and vascular inflammation is regulated by the SNS, but the neuronal control of cardiovascular inflammation remains poorly defined. Overview of this literature, our hypothesis is that there is a threshold for which we have the development of rhythm disorders in the context of low to moderate exposure and that this cardiac pathology is due to a dysfunction of the sympathetic nervous system at long-term. The objective of this thesis will be to evaluate the effects of low to moderate doses of gamma ionizing radiation in the more or less long term on the development of rhythm disturbances in conditions of whole body exposure (50mGy, 250mGy, 500mGy, 1000mGy and 2000Gy) at 50mGy/min. The 4h, 24h and 3 months post-exposure will allow the identification of early and intermediate mechanisms by blood and heart samples for molecular and histological studies (Western blot, PCR, ELISA, Immunomarkers) as well as cellular, molecular and signaling pathways that may be involved in cardiac remodeling processes in the short term. The long post-exposure time will allow the monitoring of a possible cardiac dysfunction, in particular a rhythm disorder, by Doppler ultrasound as well as the structural characterization of the heart by targeting the sympathetic nervous system. This project will allow (1) to identify a potential threshold for the appearance of deleterious structural and functional effects at the cardiac level (2) to identify the early mechanisms, in particular the signaling pathways on a healthy heart after exposure to low to moderate doses that could lead in the long term to dysregulation of the cardiac function.