Anales RANF

P.103 POSTNATAL SUBVENTRICULAR ZONE NEUROGENESIS: ADENOSINE A2A RECEPTORS AS REGULATORS OF BRAIN- DERIVED NEUROTROPHIC FACTOR Filipa F. Ribeiro 1 , Filipa Ferreira 1 1,2 , Rui Rodrigues 1,2 , Rita Soares 2 , Sandra H. Vaz, 1,2 , Susana Solá 3 , Helena Mira 4 , Ana M. Sebastião 1,2 , Sara Xapelli 1,2 1 Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; 2 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; 3 iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal; 4 Instituto de Biomedicina de Valencia (IBV-CSIC), Valencia, Spain. Constitutive neurogenesis takes place in both adult mammalian subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus (DG) in the hippocampus. This study evaluated whether adenosine A 2A receptors (A 2A Rs) have a role in postnatal SVZ neurogenesis and if they are required for brain-derived neurotrophic factor (BDNF)-induced neurogenesis, namely in cell proliferation and neuronal differentiation, and for the capacity of progenitor cells to divide and self-renew within the SVZ. Results using SVZ-derived neurosphere cultures demonstrated that neither A 2A R agonist (CGS21680, 30 nM), A 2A R antagonist (ZM241385, 50 nM) nor BDNF (30ng/ml), altered cell viability (measured by propidium iodide staining). A cell-fate study was also performed using an immunocytochemistry against Sox2 (a marker of neural stem cells with the ability to self-renew). Neither A 2A R activation nor blockade changed the number of Sox2+/+ SVZ cell-pairs derived from a progenitor cell division. Furthermore, neither proliferation (measured by BrdU staining) nor neuronal differentiation (measured by NeuN staining) of cultured cells were affected by either A 2A R agonist or antagonist incubation alone. Importantly, the in vitro data was corroborated in an in vivo 6-week-old rat model, where CGS 21680 (100 nM) was intraventricularly delivered for 28 days and BrdU was administered in the first 3 days of the treatment. In fact, A 2A R activation did not change proliferation nor neuronal differentiation (measured by BrdU and NeuN double-staining) in vivo . Nevertheless, BDNF enhancement of cell proliferation and neuronal differentiation in vitro was completely prevented by A 2A R antagonist. Conversely, A 2A R agonist enhanced axonal and dendritic length and branching of SVZ-derived neurons. Taken together, data here described reveal a novel role for A 2A Rs as modulators of SVZ neurogenesis. Contrary to hippocampal neurogenesis (S. Xapelli – oral session), A 2A R activation in the SVZ does not increase neurogenesis, only promotes axonal and dendritic growth. However, A 2A R endogenous activation is crucial for BDNF-mediated actions.