Intertwining extracellular nucleotides and their receptors with Ca2+ in determining adult neural stem cell survival, proliferation and final fate

In the central nervous system (CNS), during both brain and spinal cord development, purinergic and pyrimidinergic signalling molecules (ATP, UTP and adenosine) act synergistically with peptidic growth factors in regulating the synchronized proliferation and final specification of multipotent neural stem cells (NSCs) to neurons, astrocytes or oligodendrocytes, the myelin-forming cells. Some NSCs still persist throughout adulthood in both specific ‘neurogenic’ areas and in brain and spinal cord parenchyma, retaining the potentiality to generate all the three main types of adult CNS cells.OnceCNS anatomical structures are defined, purinergic molecules participate in calcium-dependent neuronto-gliacommunication and also control the behaviour of adultNSCs. Afterdevelopment, some purinergic mechanisms are silenced, but can be resumed after injury, suggesting a role for purinergic signalling in regeneration and selfrepairalsoviathe reactivationof adultNSCs. In this respect, at least threedifferent types of adult NSCs participate in the response of the adult brain and spinal cord to insults: stem-like cells residing in classical neurogenic niches, in particular, in the ventricular-subventricular zone (V-SVZ), parenchymal oligodendrocyte precursor cells (OPCs, also known as NG2-glia) and parenchymal injuryactivated astrocytes (reactive astrocytes). Here, we shall review and discuss the purinergic regulation of these three main adult NSCs, with particular focus on howand to what extent modulation of intracellular calcium levels by purinoceptors is mandatory to determine their survival, proliferation and final fate. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’.