Skin-derived precursors differentiating into dopaminergic neuronal cells in the brains of Parkinson disease model rats

J Neurosurg. 2010 Sep;113(3):648-55. doi: 10.3171/2010.2.JNS091432.

Abstract

Object: In the authors' previous study, they observed that amino acids 157-171 of von Hippel-Lindau protein (VHL peptide) induced neuronal differentiation of skin-derived precursors. They also noted that transplantation of these differentiated cells into the striata of a Parkinson disease (PD) rat model reduced apomorphine-induced rotations. In the present study, they investigated if these cells produce dopamine in the striatum.

Methods: Skin-derived precursors were differentiated into neurons using VHL peptide and transplanted into the striata of a PD model of rats. Four weeks after transplantation, a probe was inserted into rat striata and extracellular dopamine was extracted by microdialysis. Dopamine levels were measured by high-pressure liquid chromatography. Brain sections were assessed by immunohistochemical analysis for the presence of tyrosine hydroxylase and dopamine transporter.

Results: Increased dopamine levels in the striata of the rats were observed after transplantation (p < 0.01), and these were correlated with a reduction in the number of apomorphine-induced rotations (p < 0.05). Skin-derived precursors observed along the tract of transplantation were positive for tyrosine hydroxylase and dopamine transporter.

Conclusions: This study suggests that transplantation of skin-derived precursors, differentiated into neuronal cells using VHL peptide, can improve PD-like symptoms by enabling production of dopamine in the striata in a PD model of rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Corpus Striatum / metabolism
  • Corpus Striatum / surgery
  • Dopamine / metabolism*
  • Extracellular Space / metabolism
  • Male
  • Neurogenesis / physiology
  • Neurons / physiology*
  • Oxidopamine
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / physiopathology*
  • Parkinsonian Disorders / surgery*
  • Rats
  • Rats, Wistar
  • Recovery of Function / physiology
  • Skin / cytology*
  • Skin Physiological Phenomena
  • Stem Cell Transplantation*
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism

Substances

  • Oxidopamine
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Dopamine