Modulation of Dopaminergic Neuronal Differentiation from Sympathoadrenal Progenitors

Abstract

The capacity of sympathoadrenal progenitors from adrenal medulla to generate dopaminergic neurons in vitro makes them an attractive source for replacement therapies of neurodegenerative diseases such as Parkinson's disease. Dopaminergic cells constitute one percent of the adult adrenal medulla only. Thus, isolation of sympathoadrenal progenitors and enhancement of their capacity to derive dopaminergic neurons is a strategy to be considered. Here, we summarize data on the characterization and isolation of sympathoadrenal progenitors from adult adrenal medulla capable to give rise to functional dopaminergic neurons, in vitro. Pretransplantation treatment of these cells with pharmacological means is an important prerequisite to improve dopaminergic differentiation and efficient engraftment of sympathoadrenal progenitors. Treatment of these cells with retinoic and ascorbic acids significantly increased dopamine secretion from derived neurons. Furthermore, inhibition of Notch signaling activated molecular mechanisms involved in the determination of dopaminergic neuronal subtype. Taken together, somatic adrenomedullary sympathoadrenal progenitor cells are a valid cell source for replacement therapies with a high potential for dopaminergic neuronal differentiation.