Functional, behavioural and molecular characterization of a presymptomatic model of Parkinson disease expressing α-synuclein in the locus coeruleus

Parkinson’s disease (PD) is a neurodegenerative process characterized by the presence of Lewy bodies in different brain regions, affection of many neurotransmitter systems and manifestation of motor and nonmotor symptoms. These latter ones often appear before the motor symptomatology and highly impact on the life quality of the patients. Interestingly, the locus coeruleus (LC) that contains the highest density of noradrenergic neurons in the brain, is among the brain stem areas first displaying Lewy bodies in the disease, and is associated with prodromal non-motor symptoms. Despite its small size, it projects to almost all brain areas and exerts a key influence on the homeostasis of dopaminergic networks. The aim of this study is to examine the noradrenergic disfunction in PD. For that, we studied the impact of alpha-synuclein overexpression in the LC at molecular, functional, and behavioural levels in a pre-symptomatic rodent model of PD. Through these data, we can gain a better understanding of how noradrenergic dysregulation occurs at the earliest stages of PD, and identify potential therapeutic strategies to dampen PD progression.