Molecular medicine reports

Directed differentiation of postnatal hippocampal neural stem cells generates nuclear receptor related‑1 protein‑ and tyrosine hydroxylase‑expressing cells.

PMID 27432537


Parkinson's disease (PD) is a severe neurodegenerative disorder. Although the detailed underlying molecular mechanism remains to be elucidated, the major pathological feature of PD is the loss of dopaminergic (DA) neurons of the substantia nigra. The use of donor stem cells to replace DA neurons may be a key breakthrough in the treatment of PD. In the present study, the growth kinetics of hippocampal neural stem cells (Hip‑NSCs) isolated from postnatal mice and cultured inxa0vitro were observed, specifically the generation of cells expressing DA neuronal markers nuclear receptor related‑1 protein (Nurr1) and tyrosine hydroxylase (TH). It was revealed that Hip‑NSCs differentiated primarily into astrocytes when cultured in serum‑containing medium. However, in low serum conditions, the number of βIII tubulin‑positive neurons increased markedly. The proportion of Nurr1‑positive cells and TH‑positive neurons, significantly increased with increasing duration of directed differentiation of Hip‑NSCs (P=0.0187 and 0.0254, respectively). The results of the present study reveal that Hip‑NSCs may be induced to differentiate inxa0vitro into neurons expressing Nurr1 and TH, known to be critical regulators of DA neuronal fate. Additionally, their expression may be necessary to facilitate neuronal maturation inxa0vitro. These data suggest that Hip‑NSCs may serve as a source of DA neurons for cell therapy in patients diagnosed with PD.