title: Dopamine controls neurogenesis in the adult salamander midbrain in homeostasis and during regeneration of dopamine neurons.
abstract: Appropriate 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.
authors.affiliation: Department of Cell and Molecular Biology and Center of Developmental Biology for Regenerative Medicine (DBRM), Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Berg
authors.forename: Matthew
authors.initials: M
authors.lastname: Kirkham
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.forename: Jonas
authors.initials: J
authors.lastname: Frisén
authors.forename: András
authors.initials: A
authors.lastname: Simon
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D004298:Dopamine / Q000502:physiology*; D006706:Homeostasis; D008636:Mesencephalon / Q000502:physiology*; D009416:Nerve Regeneration; D055495:Neurogenesis; D009474:Neurons; D010300:Parkinson Disease; D013234:Stem Cells / Q000166:cytology; D014562:Caudata / Q000502:physiology
chemical_list: D004298:Dopamine