Benito, M. 1 , Matute, C. 1 & Cavaliere, F. 1
1 Departamento de Neurociencias, Universidad del País Vasco-UPV/EHU, Leioa, Spain
2
Excitotoxic concentration of extracellular purines is among the factors inhibiting adult neurogenesis during neurodegenerative diseases. We previously demonstrated extracellular ATP released during ischemia inhibited adult neurogenesis from subventricular zone (SVZ) through the activation of specific P2X receptors. Here we wanted to study the effect of adenosine, the natural product of ATP hydrolysis, in modulating neurogenesis from the SVZ. We demonstrated by immunofluorescence and citofluorimetry that high concentration of adenosine reduces neuronal differentiation of neurospheres cultures generated from postnatal SVZ. All the adenosine receptors (A1, A2a, A2b and A3) are expressed in this cells but only A1 is involved in the inhibition of neuronal differentiation, as demonstrated by qRT-PCR, Western blot and specific gene silencing, through downregulation of a multitude of genes related with neurogenesis.
We found that the mechanism by which adenosine inhibits neuronal differentiation involves the release of IL10 and further activation of the Bmp2/SMAD3 pathway sustaining indeed astrogliogenesis.
In vitro data were confirmed also in in vivo neurogenesis. After intra cerebral ventricular infusion of the A1 agonist CPA we found a drastic reduction of neurogenesis and the parallel increase of astrogliogenesis in the olfactory bulb of adult rats. With this work we contribute to the knowledge of the purinergic mechanisms that regulate adult neurogenesis, especially in pathological condition when purines are released at citotoxic concentrations.