PhD Student: Jérémy Pépin

Abstract

Huntington's disease (HD) is a inherited neurodegenerative disease affecting the brain. This disease is characterized by clinical symptoms such as psychiatric, cognitive and motor disorders worsening over time. These deficiencies are due to an abnormal increase in the size of the CAG repeats in the gene encoding the huntingtin protein. Thisaccumulates in the brain cells and causes their death. Previous studies have shown that the metabolic profile measured in ¹H NMR spectroscopy can be altered in patients with this disease as well as major atrophy of certain structures of the brain. Hypotheses involving defects in energy metabolism have been advanced to explain partially the pathophysiology of the disease. The metabolic actors could thus be biomarkers of interest. Using a promising MRI modality called Chemical Exchange Saturation Transfer (CEST), it is possible to detect low-concentrated labile protons that are classically undetectable in MRI. It thus becomes possible to map in vivo the distribution of metabolites such as glutamate (which is a neurotransmitter) or glucose (which is the fuel of cells) which are potentially involved in neurodegenerative diseases. The methodological developments carried out during this thesis were then applied to rodent models of Huntington's disease (KI140 mice, R6/1 mice, BACHD rats) in order to identify potential biomarkers of the pathology and to evaluate the relevance of these innovative MRI methods. All of these results and methods implemented during this thesis show the potential of CEST imaging for the study of neurodegenerative diseases.