Role of heparin binding growth factors in nigrostriatal dopamine system development and Parkinson's disease

Deanna M. Marchionini, Elin Lehrmann, Yaping Chu, Bin He, Caryl E. Sortwell, Kevin G. Becker, William J. Freed, Jeffrey H. Kordower, Timothy J. Collier

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

The developmental biology of the dopamine (DA) system may hold important clues to its reconstruction. We hypothesized that factors highly expressed during nigrostriatal development and re-expressed after injury and disease may play a role in protection and reconstruction of the nigrostriatal system. Examination of gene expression in the developing striatum suggested an important role for the heparin binding growth factor family at time points relevant to establishment of dopaminergic innervation. Midkine, pleiotrophin (PTN), and their receptors syndecan-3 and receptor protein tyrosine phosphatase β/ζ, were highly expressed in the striatum during development. Furthermore, PTN was up-regulated in the degenerating substantia nigra of Parkinson's patients. The addition of PTN to ventral mesencephalic cultures augmented DA neuron survival and neurite outgrowth. Thus, PTN was identified as a factor that plays a role in the nigrostriatal system during development and in response to disease, and may therefore be useful for neuroprotection or reconstruction of the DA system.

Original languageEnglish (US)
Pages (from-to)77-88
Number of pages12
JournalBrain Research
Volume1147
Issue number1
DOIs
StatePublished - May 25 2007
Externally publishedYes

Keywords

  • Development
  • HB-GAM
  • Human
  • Microarray
  • Parkinson's disease
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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