Adult Neurogenesis In The Subventricular Zone: Studies On The Role Of Purinergic Signalling

The subventricular zone (SVZ) of the lateral ventricles is one of the two neurogenic region persisting in the adult brain. Within the SVZ, astrocyte-like stem cells give rise to clusters of transit-amplifying progenitors, which, in turn, generate migrating neuroblasts. Stem and progenitor cells can be grown as neurospheres (NS) in vitro and increasing (albeit still initial) evidence suggests that nucleotides can control their proliferation, self-renewal, and differentiation. With the present study, we aimed at investigating the role of ADPβS, a P2Y1,12,13 receptor agonist, in modulating adult neurogenesis in the mouse SVZ both in vitro, and in vivo. When cells derived from the dissociation of secondary NS were plated in presence of ADPβS in vitro, an increased number of tertiary NS was observed, which was paralleled by a reduction of their size and of the total number of viable cells. No changes in the progression through the cell cycle were detected. Since progenitor cells have limited proliferative and self-renewal capacity with respect to stem cells, and therefore give rise to small-sized neurospheres, it can be envisaged that ADPβS acts specifically on progenitor cells. Moreover, ADPβS stimulated cell differentiation in undissociated neurospheres, resulting in the increased appearance of both astrocytic (GFAP) and neuronal (βTUB) markers. The i.c.v. administration of ADPβS in vivo increased GFAP immunostaining and promoted the generation of newborn neuroblasts expressing the typical marker doublecortin, thus confirming the in vitro results. ADPβS-induced hypertrophy of the SVZ was also observed. Taken together, our data suggest that nucleotides can be useful in implementing the self-renewal ability of the damaged brain.