Dopamine Controls Neurogenesis in the Adult Salamander Midbrain in Homeostasis and during Regeneration of Dopamine Neurons

SummaryAppropriate termination of regenerative processes is critical for producing the correct number of cells in tissues. Here we provide evidence for an end-product inhibition of dopamine neuron regeneration that is mediated by dopamine. Ablation of midbrain dopamine neurons leads to complete regeneration in salamanders. Regeneration involves extensive neurogenesis and requires activation of quiescent ependymoglia cells, which express dopamine receptors. Pharmacological compensation for dopamine loss by L-dopa inhibits ependymoglia proliferation and regeneration in a dopamine receptor-signaling-dependent manner, specifically after ablation of dopamine neurons. Systemic administration of the dopamine receptor antagonist haloperidol alone causes ependymoglia proliferation and the appearance of excessive number of neurons. Our data show that stem cell quiescence is under dopamine control and provide a model for termination once normal homeostasis is restored. The findings establish a role for dopamine in the reversible suppression of neurogenesis in the midbrain and have implications for regenerative strategies in Parkinson's disease.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (421 K)Download as PowerPoint slideHighlights► Regeneration of midbrain dopamine neurons depends on decreased dopamine signaling ► L-dopa inhibits ependymoglia cell proliferation during dopamine neuron regeneration ► Proliferation of ependymoglia cells is constantly suppressed by dopamine signaling ► Inhibition of dopamine signaling evokes neurogenesis by quiescent ependymoglia cells