| First Author | Zhang W | Year | 2018 |
| Journal | J Biol Chem | Volume | 293 |
| Issue | 40 | Pages | 15641-15651 |
| PubMed ID | 30139740 | Mgi Jnum | J:270283 |
| Mgi Id | MGI:6268527 | Doi | 10.1074/jbc.RA118.002840 |
| Citation | Zhang W, et al. (2018) Neuron activity-induced Wnt signaling up-regulates expression of brain-derived neurotrophic factor in the pain neural circuit. J Biol Chem 293(40):15641-15651 |
| abstractText | Brain-derived neurotrophic factor (BDNF) is a master regulator of synaptic plasticity in various neural circuits of the mammalian central nervous system. Neuron activity-induced BDNF gene expression is regulated through the Ca(2+)/CREB pathway, but other regulatory factors may also be involved in controlling BDNF levels. We report here that Wnt/beta-catenin signaling plays a key role in controlling neuron activity-regulated BDNF expression. Using primary cortical cultures, we show that blockade of Wnt/beta-catenin signaling inhibits the BDNF up-regulation that is induced by activation of the N-methyl-d-aspartic acid (NMDA) receptor and that activation of the Wnt/beta-catenin signaling pathway stimulates BDNF expression. In vivo, Wnt/beta-catenin signaling activated BDNF expression and was required for peripheral pain-induced up-regulation of BDNF in the mouse spine. We also found that conditional deletion of one copy of either Wntless (Wls) or beta-catenin by Nestin-Cre-mediated recombination is sufficient to inhibit the pain-induced up-regulation of BDNF. We further show that the Wnt/beta-catenin/BDNF axis in the spinal neural circuit plays an important role in regulating capsaicin-induced pain. These results indicate that neuron activity-induced Wnt signaling stimulates BDNF expression in the pain neural circuits. We propose that pain-induced Wnt secretion may provide an additional mechanism for intercellular coordination of BDNF expression in the neural circuit. |
