Aging is associated with a degeneration of noradrenergic-, but not dopaminergic-neurons, in the short-lived killifish Nothobranchius furzeri

Abstract

SummaryParkinson’s disease (PD) is characterized by phosphorylation and aggregation of the protein α-Synuclein and ensuing neuronal death progressing from the noradrenergic locus coeruleus to midbrain dopaminergic neurons. In 2019, Matsui and colleagues reported in Cell Reports a spontaneous age-dependent degeneration of dopaminergic neurons and an even greater neurodegeneration of the noradrenergic neurons in the short-lived killifish Nothobranchius furzeri.Given the great possible relevance of a spontaneous model for PD, we set to confirm their results by whole-brain clarification and 3D nuclei reconstruction to quantify total cell numbers. We observed an age dependent neurodegeneration limited to the locus coeruleus and not involving the posterior tuberculum. In addition, we observed the presence of phospho-Synuclein in the soma of locus coeruleus neurons detectable already at a young age and increasing during aging.Our result demonstrates that N. furzeri models the early stages of PD, but not the degeneration of dopaminergic neurons.