Axonal elongation and dendritic branching is enhanced by adenosine A sub(2A) receptors activation in cerebral cortical neurons

• Published in: Brain structure & function Vol. 221; no. 5; pp. 2777 - 2799
• Main Authors: Ribeiro, Filipa F, Neves-Tome, Raquel, Assaife-Lopes, Natalia, Santos, Telma E, Silva, Rui FM, Brites, Dora, Ribeiro, Joaquim A, Sousa, Monica M, Sebastiao, Ana M
• Format: Journal Article
• Language: English
• Published: 01.06.2016
• ISSN: 1863-2653; 1863-2661
• DOI: 10.1007/s00429-015-1072-1

Axon growth and dendrite development are key processes for the establishment of a functional neuronal network. Adenosine, which is released by neurons and glia, is a known modulator of synaptic transmission but its influence over neuronal growth has been much less investigated. We now explored the action of adenosine A sub(2A) receptors (A sub(2A)R) upon neurite outgrowth, discriminating actions over the axon or dendrites, and the mechanisms involved. Morphometric analysis of primary cultures of cortical neurons from E18 Sprague-Dawley rats demonstrated that an A sub(2A)R agonist, CGS 21680, enhances axonal elongation and dendritic branching, being the former prevented by inhibitors of phosphoinositide 3-kinase, mitogen-activated protein kinase and phospholipase C, but not of protein kinase A. By testing the influence of a scavenger of BDNF (brain-derived neurotrophic factor) over the action of the A sub(2A)R agonist and the action of a selective A sub(2A)R antagonist over the action of BDNF, we could conclude that while the action of A sub(2A)Rs upon dendritic branching is dependent on the presence of endogenous BDNF, the influence of A sub(2A)Rs upon axonal elongation is independent of endogenous BDNF. In consonance with the action over axonal elongation, A sub(2A)R activation promoted a decrease in microtubule stability and an increase in microtubule growth speed in axonal growth cones. In conclusion, we disclose a facilitatory action of A sub(2A)Rs upon axonal elongation and microtubule dynamics, providing new insights for A sub(2A)Rs regulation of neuronal differentiation and axonal regeneration.