Neural Stem/progenitor Cells Differentiate in Vitro to Neurons by the Combined Action of Dibutyryl Camp and Interferon-gamma

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Publication Date

Fall 2009


Transplantation of neural stem/progenitor cells (NSPCs) is a promising strategy for repair of the diseased/injured central nervous system (CNS); however, controlling their differentiation remains a significant hurdle. This study is aimed at controlling differentiation and specifically at screening exogenous factors to direct NSPC differentiation into neurons in vitro. In this study, adult rat SVZ-derived NSPCs were treated with several factors and screened individually and in combination for changes in cellular morphology, neuronal marker expression, quantitative real-time qRT-PCR, and electrophysiological properties. These in vitro screens showed that of all the different treatments, dibutyryl cyclic AMP (dbcAMP) and interferon-gamma (IFN-γ) enhanced neuronal differentiation most significantly compared to the 1% fetal bovine serum (FBS) controls. Importantly, the combined treatment of NSPCs with dbcAMP and IFN-γ promoted greater neuronal differentiation as reflected by an increase in β-III tubulin expression and morphological differentiation. Interestingly, the neurons that were generated from the NSPCs in vitro in the presence of dbcAMP and IFN-γ, alone or in combination, responded to exogenous glutamate (Glu), but not gamma-aminobutyric acid (GABA), indicating that these neurons express glutamate receptors. These NSPC-derived neurons may be promising for neural regenerative strategies in the CNS.





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