Chronic expression of transforming growth factor-beta enhances adult neurogenesis

Abstract

Neural stem cells reside in two neurogenic regions of the adult brain: the dentate gyrus of the hippocampus (DG) and the subventricular zone (SVZ). Their proliferation, differentiation, migration and survival are modulated by intrinsic and extrinsic signals, forming a neurogenic niche. Brain cytokines have only been recently regarded as possible components of this neurogenic niche. In particular, we have demonstrated that transforming growth factor-beta (TGF-beta) has a pro-neurogenic effect in the DG in a model of increased neurogenesis by adrenalectomy. We wanted to test whether TGF-beta has a similar effect in another neurogenic region, namely the SVZ. To test this possibility, adult rats were injected with adenoviral vectors expressing TGF-beta (Ad-TGF) or beta-galactosidase (Ad-bgal) in the SVZ and neurogenesis was evaluated 3 weeks later. We have observed that chronic TGF-beta expression increased neurogenesis in the ipsilateral hemisphere of Ad-TGF but not in Ad-bgal-treated rats compared to their contralateral side. In addition, an unspecific effect of the adenoviral vector per se could not be totally discarded. We conclude, under our experimental conditions, that TGF-beta could enhance adult neurogenesis in the SVZ. This data increase the growing evidence supporting a pro-neurogenic role of anti-inflammatory cytokines in the adult brain.