Themes: Biology, medicine, health
Thesis location: Experimental Radiotoxicology and Radiobiology Laboratory (LRTOX) - Fontenay-aux-Roses (92)
Start: October 2021
Master's Degree in Toxicology or Neurobiology
Knowledge in neuroanatomy, molecular biology, animal experimentation, histology
Age limit: 26 years old unless otherwise stated.
This PhD project involves coexposure to two stress factors of different natures and is part of a scientific approach linked to the concept of exposome. This concept brings together all the substances and stresses to which an individual will be exposed from conception in utero until the end of his or her life. Our project focuses on occupational exposure factors related to activities linked to the use of nuclear energy. In this context, personnel are exposed to chemical and radiological pollutants that raise question on a potential risk to their health, including to the brain. The main cause of contamination inherent to these activities is the inhalation of particulate pollutants, of which the brain is a direct target. The aim of this project is to study the effects of chemical and radiological co-exposure on the rat brain using a proof-of-concept approach. Rats will be exposed successively to acute inhalation of tungsten aerosol at low (5 mg.m-3 based on the VLEP) or high volumic concentration (80 mg.m-3) and then to acute external gamma irradiation at 50 mGy (in the low dose range, <100 mGy according to UNSCEAR). Survival and morphological integrity of neural cells as the first indicator of brain suffering will be assessed in the neuroanatomical area called the rostral migratory stream, a neurogenic niche in adult rats. The involvement of oxidative stress will be evaluated, as well as that of neuroinflammation by monitoring the reaction of microglial cells. This objective will be studied in two stages: Objective 1: Study of the survival and morphological integrity of neural cells in the cerebral zones of interest for the different exposure groups at 28 days post-exposure (generation of proof-of-principle data). Objective 2: Development of mechanistic studies, earlier post-exposure times and molecular and cellular assessments of the involvement of target processes of neuroinflammation and oxidative stress will be implemented. The results obtained will provide new data on the combined effects of chemical and radiological coexposure in vivo. They are positioned as a methodological and scientific starting point on a mixture of stressors relevant to the exposures on which IRSN is developing its expertise.