Galanin promotes neuronal differentiation from neural progenitor cells and olfactory bulb neurogenesis

Galanin and its receptors are expressed in neural progenitors cells (NPCs) during development and in neurogenic areas in the adult brain. Galanin and GalR2 have been shown to be neuroprotective, minimizing hippocampal cell death after glutamate, kainic acid or statuosporine treatment and Aβ 1-42 toxicity in forebrain cultures. Targeted deletion of Galanin (galKO) or GalR2 has an inhibitory effect on the rate of peripheral nerve regeneration after injury. This is paralleled by deficits in neurite outgrowth in vitro. Furthermore, absence of galanin signalling in the developing embryo results in loss of particular neuronal subsets in both the central (pituitary, basal forebrain) and peripheral (dorsal root ganglia) nervous systems. This suggests a potential role for galanin in brain stem cells. However, this hypothesis remains unexplored.
In this study, we compare the proliferation and neurogenic capacity galKO and wildtype NPCs isolated from the developing striatum and from the adult subventricular zone. To date we have found that galanin increases proliferation of these progenitors in vitro. Furthermore, galKO results in a reduced neuronal differentiation from NPCs. We also analyzed the activation of AKT and p42/44 MAPK, as key signalling pathways in cell fate and the up-regulation of proneuronal and antiapoptotic genes after galanin stimulation. Interestingly, galanin disruption leads to decreased subventricular neurogenesis in the adult brain. All together, our data underline the importance of galanin in neural stem cell fate.