Dopaminergic lesion enhances growth factor-induced striatal neuroblast migration

J Neuropathol Exp Neurol. 2008 Feb;67(2):105-16. doi: 10.1097/nen.0b013e3181630cff.


Adult neurogenesis persists in the subventricular zone and is decreased in Parkinson disease (PD). The therapeutic potential of neurogenesis in PD requires understanding of mechanisms of 1) neural stem cell generation; 2) their guidance to the lesion site; and 3) the environment that enables neuronal differentiation, survival, and functional integration. We examined the combined intraventricular infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2) in a 6-hydroxydopamine-induced rodent model of PD. Epidermal growth factor and FGF-2 induced a massive increase in cell proliferation and in numbers of doublecortin-expressing neuroblasts in the subventricular zone. These growth factors also increased dopaminergic neurogenesis in the olfactory bulb and promoted the migration of newly generated neuroblasts from the subventricular zone into the adjacent striatum. The effects of EGF and FGF-2 were present in unlesioned animals but were dramatically enhanced in 6-hydroxydopamine-lesioned animals. These findings suggest that newly generated neuroblasts may be redirected to the region of dopaminergic deficit, and that EGF and FGF-2 can enhance dopaminergic neurogenesis in the olfactory bulb but not in the striatum. Similar mechanisms may be involved in the increased numbers of dopaminergic neurons observed in the olfactory bulbs of PD patients and their functional olfactory deficits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / chemically induced
  • Brain Injuries / drug therapy*
  • Brain Injuries / pathology*
  • Brain Injuries / physiopathology
  • Cell Count
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Proliferation / drug effects
  • Corpus Striatum / drug effects
  • Corpus Striatum / pathology*
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Female
  • In Situ Nick-End Labeling
  • Intercellular Signaling Peptides and Proteins / administration & dosage*
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Oxidopamine
  • Rats
  • Rats, Wistar


  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Oxidopamine
  • Dopamine