Differentiation of hippocampal stem cells into functional neurons: evolving our understanding of monoamine oxidase-A inhibition.

Depression affects many millions of people worldwide and much is still unknown with respect to the mode of action of antidepressant drugs. The hippocampus has been associated with many psychiatric disorders, including clinical depression. Recently, stem cells have also been shown to reside within discrete regions of the hippocampus and can differentiate under a variety of conditions into neural cells. In this issue, Chiou et al. have elegantly demonstrated that cells isolated from the rat hippocampus, and treated with the antidepressant moclobemide, may be differentiated in vitro into neural cells exhibiting features to those of serotoninergic neurons. They have also suggested that this process was mediated, in part, through the expression of specific antiapoptotic genes (Bcl-2 and Bcl-XL) and via activation of extracellular-regulated kinase. This work raises the attractive possibility that the use of antidepressants, such as moclobemide, may exert neuroprotective and potentially neurogenerative effects not just in vitro, but also in vivo, through the selected differentiation of stem cells into functional neurons. The exact mechanisms by which such antidepressants differentiate neural stem cells still remains to be fully elucidated.