Axonal elongation and dendritic branching is enhanced by adenosine A2A receptors activation in cerebral cortical neurons

• Published in: Brain structure & function Vol. 221; no. 5; pp. 2777 - 2799
• Main Authors: Ribeiro, Filipa F., Neves-Tomé, Raquel, Assaife-Lopes, Natália, Santos, Telma E., Silva, Rui F. M., Brites, Dora, Ribeiro, Joaquim A., Sousa, Mónica M., Sebastião, Ana M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2016
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine A2 Receptor Agonists - pharmacology; Animals; Axons - drug effects; Axons - physiology; Biomedical and Life Sciences; Biomedicine; Brain-Derived Neurotrophic Factor - metabolism; Cell Biology; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Dendrites - drug effects; Dendrites - physiology; MAP Kinase Signaling System - drug effects; Microtubules - drug effects; Microtubules - physiology; Neurites - drug effects; Neurites - physiology; Neurology; Neurons - cytology; Neurons - drug effects; Neurons - physiology; Neurosciences; Original Article; Phenethylamines - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2A - physiology; Receptor, trkB - metabolism; Microtubule dynamics; Axonal growth; BDNF; Cortical primary cultures; Neurite outgrowth
• DOI: 10.1007/s00429-015-1072-1
• ISSN: 1863-2653

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 2A receptors (A 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 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 2A R agonist and the action of a selective A 2A R antagonist over the action of BDNF, we could conclude that while the action of A 2A Rs upon dendritic branching is dependent on the presence of endogenous BDNF, the influence of A 2A Rs upon axonal elongation is independent of endogenous BDNF. In consonance with the action over axonal elongation, A 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 2A Rs upon axonal elongation and microtubule dynamics, providing new insights for A 2A Rs regulation of neuronal differentiation and axonal regeneration.