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

Abstract

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. 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. 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. 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.