Inducing dopaminergic differentiation of expanded rat mesencephalic neural stem cells by ascorbic acid in vitro *

Abstract

Abstract Ascorbic acid (AA) induced differentiation of neural stem cells (NSCs) into dopaminergic (DAergic) neurons is reported. NSCs derived from rat mesencephalon were maintained and expanded in a defined medium containing mitogens of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Compared with the control, ascorbic acid treatment led to more DAergic neuronal differentiation as indicated by the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT), which are specific markers of dopamine neurons. AA induction also enhanced expression of Nurrl and Shh. PD98059, an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, couldblock AA-induced Nurrl, TH and DAT mRNA expression. The results might suggest a new strategy to provide enough dopaminergic cells for the therapy of Parkinson's disease (PD), and Nurrl and ERK signaling pathway might participate in the AA-induced DAergic differentiation.