Galanin promotes neuronal differentiation from neural progenitor cells in vitro and contributes to the generation of new olfactory neurons in the adult mouse brain

Abstract

Galanin is a pleiotropic neuropeptide widely expressed in the nervous system. It plays a role in many diverse physiological functions – including nociception, cognition and metabolism regulation – and acts as neurotrophic/neuroprotective factor for several neuronal populations. In this article we sought to determine the role of galanin on neural stem cell function and its contribution to the plasticity of the nervous system. Here we show that galanin and its receptors are expressed in neural progenitor cells (NPCs) isolated from the developing striatum. Stimulation with galanin results in upregulation of Bcl-Xl, Bcl-2, Mash-1 and Olig-2 that are part of well known pro-survival/pro-neuronal signalling pathways. Accordingly, treatment with galanin increases the number of neurons upon differentiation from these progenitors. We then show that these effects are recapitulated in NPCs isolated from the adult subventricular zone (SVZ), where galanin increases the total number of neurons and the number of newly-generated neurons upon differentiation in vitro. The significance of these findings is highlighted in the adult brain where loss of galanin leads to a marked decrease in the rate of adult SVZ neurogenesis and a reduction in the number of newly generated cells in the olfactory bulb. Interestingly, Gal-KO mice display normal performances in simple tasks of olfactory detection and discrimination, which points to the existence of a certain degree of redundancy in SVZ neurogenesis. Our findings establish the role of galanin as a modulator of neural stem cell function and support the importance of galanin for brain plasticity and repair.