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

Summary Parkinson’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.