Evidence for neurogenesis in the adult mammalian substantia nigra

Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7925-30. doi: 10.1073/pnas.1131955100. Epub 2003 Jun 5.


New neurons are generated from stem cells in a few regions of the adult mammalian brain. Here we provide evidence for the generation of dopaminergic projection neurons of the type that are lost in Parkinson's disease from stem cells in the adult rodent brain and show that the rate of neurogenesis is increased after a lesion. The number of new neurons generated under physiological conditions in substantia nigra pars compacta was found to be several orders of magnitude smaller than in the granular cell layer of the dentate gyrus of the hippocampus. However, if the rate of neuronal turnover is constant, the entire population of dopaminergic neurons in substantia nigra could be replaced during the lifespan of a mouse. These data indicate that neurogenesis in the adult brain is more widespread than previously thought and may have implications for our understanding of the pathogenesis and treatment of neurodegenerative disorders such as Parkinson's disease.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • Antimetabolites / pharmacology
  • Apoptosis
  • Bromodeoxyuridine / pharmacology
  • Dopamine / metabolism
  • Dopamine Agents / pharmacology
  • Hippocampus / pathology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Neurons / metabolism*
  • Neurons / pathology
  • Parkinson Disease / pathology
  • Stem Cells / metabolism
  • Substantia Nigra / anatomy & histology*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology*
  • Synapses
  • Time Factors


  • Antimetabolites
  • Dopamine Agents
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Bromodeoxyuridine
  • Dopamine