Nurr1-induced dopaminergic differentiation from rat fetal neural precursor cells

Abstract

In-vitro expanded CNS precursors provide a potentially unlimited source of dopamine (DA) neurons for the experimental treatment in Parkinson`s disease. The nuclear orphan receptor Nurr1 is essential for the development of midbrain DA neurons in vivo. Here, we demonstrate the ability of Nurr1 to convert naive CNS precursors into DA neurons independent of their gestational age or brain region of origin. Nurr1-induced DA neurons exhibited depolarization-evoked DA release in vitro. However, Nurr1-induced DA neurons displayed less mature morphologies and lower levels of DA production than those obtained from primary midbrain precursors. Upon transplantation into Parkinsonian rats, Nurr1-induced DA neurons showed low survival rates and limited in vivo differentiation. No improvement in apomorphine-induced rotation behavior was detected. These results demonstrate that Nurr1 induces components of DA neuron function in naive CNS precursors. However, additional factors will be required to achieve in vivo function and fulfill the promise of CNS precursor-based cell therapy in Parkinson`s disease.