Neuron activity-induced Wnt signaling up-regulates expression of brain-derived neurotrophic factor in the pain neural circuit

Wenping Zhang, Yuqiang Shi, Yanxi Peng, Ling Zhong, Shuang Zhu, Wenbo Zhang, Shao Jun Tang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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 Ca2+/CREB pathway, but other regulatory factors may also be involved in controlling BDNF levels. We report here that Wnt/ β -catenin signaling plays a key role in controlling neuron activity-regulated BDNF expression. Using primary cortical cultures, we show that blockade of Wnt/ β -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/ β -catenin signaling pathway stimulates BDNF expression. In vivo, Wnt/ β - 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 β -catenin by Nestin-Cre- mediated recombination is sufficient to inhibit the pain-induced up-regulation of BDNF. We further show that the Wnt/ β-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.

Original languageEnglish (US)
Pages (from-to)15641-15651
Number of pages11
JournalJournal of Biological Chemistry
Volume293
Issue number40
DOIs
StatePublished - Oct 5 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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