Molecular and signaling mechanisms induced by oxidative stress in a Drosophila in vivo model of Parkinson's disease : paraquat intoxication and alpha-synuclein expression
Parkinson's disease (PD) is well characterized as a neurodegenerative disease with progressive loss of dopaminergic neurons (DAn) from substantia nigra, a subcortical structure of the basal ganglia. Most of time, PD is sporadic but it is known that exposure to environmental toxins like pesticides or mutations of genes like -synuclein can cause PD. -syncuclein is the main component of Lewy's bodies, which are cytoplasmic inclusions present in DAn in PD. During my Ph.D., I focused first on the study of paraquat (PQ) neurotoxicity, a strong oxidative stress generator involved in PD. Our results show that PQ toxicity can be triggered by dopamine signaling trough a D1-like dopamine receptor known mainly for its involvement in memory processes in Drosophila. Inactivation of this receptor in glutamatergic neurons was found to be protective against PQ toxicity in Drosophila. Later, I focused on the study of a-synuclein neurotoxicity and its relationship with oxidative stress. This led to the development of a whole Drosophila central nervous system explants culture technique that allowed study of a-synuclein effects on vesicular dynamic along the axons of DAn through FRAP experiments. This study led to a better understanding of the relationships between DA and oxidative stress in the PD's pathogenesis