Neuron activity–induced Wnt signaling up-regulates expression of brain-derived neurotrophic factor in the pain neural circuit
Open accessAbstract
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/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.
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BDNF upregulation induced by synaptic activity depends on Wnt secretion.
“FosB and CREB can regulate BDNF expression, and BDNF upregulation induced by synaptic activity depends on Wnt secretion [125].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [125]
FosB and CREB can regulate BDNF expression.
“FosB and CREB can regulate BDNF expression, and BDNF upregulation induced by synaptic activity depends on Wnt secretion [125].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [125]
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The molecular and cellular mechanisms of depression: a focus on reward circuitry
Fox, M. E., & Lobo, M. K. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0415-3 · Cited by 232 · see citing works
- Authors
- Zhang, W., Shi, Y., Peng, Y., Zhong, L., Zhu, S., Zhang, W., & Tang, S.-J.
- Affiliations
- Zhejiang Sci-Tech University (CN)
- The University of Texas Medical Branch at Galveston (US)
- Sun Yat-sen University (CN)
- Corresponding author
- Tang, Shao-Jun
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 293
- Issue
- 40
- Pages
- 15641-15651
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC6177598
- OpenAlex
- W2888731457
- Cited by
- 59
- References
- 43
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 13 · 2022: 12 · 2021: 8 · 2020: 8 · 2019: 1
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) (R01NS079166, R01NS095747)
- HHS | NIH | National Institute on Drug Abuse (NIDA) (R01DA036165)
- HHS | NIH | National Eye Institute (NEI) (R01EY026629)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- brain-derived neurotrophic factor, Wnt/β-catenin signaling, neuronal activity, spinal cord, NMDA receptor, Wntless, β-catenin, capsaicin-induced pain, synaptic plasticity
- MeSH terms
- Animals, Azepines, Benzamides, Capsaicin, Cerebral Cortex, Embryo, Mammalian, Gene Expression Regulation, Hindlimb, Male, Mice, Inbred C57BL, Neuronal Plasticity, Neurons, Pain, Spinal Cord, Anti-Anxiety Agents, Transcription, Genetic, Receptors, N-Methyl-D-Aspartate, Mice, Knockout, Brain-Derived Neurotrophic Factor, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins, beta Catenin, Mice, Wnt Signaling Pathway, Wnt3A Protein, Primary Cell Culture
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