| First Author | Kharebava G | Year | 2015 |
| Journal | Biol Open | Volume | 4 |
| Issue | 12 | Pages | 1660-70 |
| PubMed ID | 26545965 | Mgi Jnum | J:227120 |
| Mgi Id | MGI:5699769 | Doi | 10.1242/bio.013425 |
| Citation | Kharebava G, et al. (2015) N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons. Biol Open 4(12):1660-70 |
| abstractText | Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3) that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1) transcription and sonic hedgehog (Shh) target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO) agonist (SAG) or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway. |
