The more you have, the less you get: the functional role of inflammation on neuronal differentiation of endogenous and transplanted neural stem cells in the adult brain.

The differentiation of neural stem cells toward a neuronal phenotype is determined by the extracellular and intracellular factors that form the neurogenic niche. In this review, we discuss the available data on the functional role of inflammation and in particular, pro- and anti-inflammatory cytokines, on neuronal differentiation from endogenous and transplanted neural stem/progenitor cells. In addition, we discuss the role of microglial cell activation on these processes and the fact that microglial cell activation is not univocally associated with a pro-inflammatory milieu. We conclude that brain cytokines could be regarded as part of the endogenous neurogenic niche. In addition, we propose that accumulating evidence suggests that pro-inflammatory cytokines have a negative effect on neuronal differentiation, while anti-inflammatory cytokines exert an opposite effect. The clarification of the functional role of cytokines on neuronal differentiation will be relevant not only to better understand adult neurogenesis, but also to envisage complementary treatments to modulate cytokine action that could increase the therapeutic benefit of future progenitor/stem cell-based therapies.