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Antillatoxin-Stimulated Neurite Outgrowth Involves the Brain-Derived Neurotrophic Factor (BDNF) - Tropomyosin Related Kinase B (TrkB) Signaling Pathway.

Publication ,  Journal Article
Mehrotra, S; Pierce, ML; Cao, Z; Jabba, SV; Gerwick, WH; Murray, TF
Published in: Journal of natural products
March 2022

Voltage-gated sodium channel (VGSC) activators promote neurite outgrowth by augmenting intracellular Na+ concentration ([Na+]i) and upregulating N-methyl-d-aspartate receptor (NMDAR) function. NMDAR activation stimulates calcium (Ca2+) influx and increases brain-derived neurotrophic factor (BDNF) release and activation of tropomyosin receptor kinase B (TrkB) signaling. The BDNF-TrkB pathway has been implicated in activity-dependent neuronal development. We have previously shown that antillatoxin (ATX), a novel lipopeptide isolated from the cyanobacterium Moorea producens, is a VGSC activator that produces an elevation of [Na+]i. Here we address the effect of ATX on the synthesis and release of BDNF and determine the signaling mechanisms by which ATX enhances neurite outgrowth in immature cerebrocortical neurons. ATX treatment produced a concentration-dependent release of BDNF. Acute treatment with ATX also resulted in increased synthesis of BDNF. ATX stimulation of neurite outgrowth was prevented by pretreatment with a TrkB inhibitor or transfection with a dominant-negative Trk-B. The ATX activation of TrkB and Akt was blocked by both a NMDAR antagonist (MK-801) and a VGSC blocker (tetrodotoxin). These results suggest that VGSC activators such as the structurally novel ATX may represent a new pharmacological strategy to promote neuronal plasticity through a NMDAR-BDNF-TrkB-dependent mechanism.

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Published In

Journal of natural products

DOI

EISSN

1520-6025

ISSN

0163-3864

Publication Date

March 2022

Volume

85

Issue

3

Start / End Page

562 / 571

Related Subject Headings

  • Tropomyosin
  • Signal Transduction
  • Receptors, N-Methyl-D-Aspartate
  • Peptides, Cyclic
  • Neuronal Outgrowth
  • Medicinal & Biomolecular Chemistry
  • Lipopeptides
  • Brain-Derived Neurotrophic Factor
  • 4208 Traditional, complementary and integrative medicine
  • 11 Medical and Health Sciences
 

Citation

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Mehrotra, S., Pierce, M. L., Cao, Z., Jabba, S. V., Gerwick, W. H., & Murray, T. F. (2022). Antillatoxin-Stimulated Neurite Outgrowth Involves the Brain-Derived Neurotrophic Factor (BDNF) - Tropomyosin Related Kinase B (TrkB) Signaling Pathway. Journal of Natural Products, 85(3), 562–571. https://doi.org/10.1021/acs.jnatprod.1c01001
Mehrotra, Suneet, Marsha L. Pierce, Zhengyu Cao, Sairam V. Jabba, William H. Gerwick, and Thomas F. Murray. “Antillatoxin-Stimulated Neurite Outgrowth Involves the Brain-Derived Neurotrophic Factor (BDNF) - Tropomyosin Related Kinase B (TrkB) Signaling Pathway.Journal of Natural Products 85, no. 3 (March 2022): 562–71. https://doi.org/10.1021/acs.jnatprod.1c01001.
Mehrotra S, Pierce ML, Cao Z, Jabba SV, Gerwick WH, Murray TF. Antillatoxin-Stimulated Neurite Outgrowth Involves the Brain-Derived Neurotrophic Factor (BDNF) - Tropomyosin Related Kinase B (TrkB) Signaling Pathway. Journal of natural products. 2022 Mar;85(3):562–71.
Mehrotra, Suneet, et al. “Antillatoxin-Stimulated Neurite Outgrowth Involves the Brain-Derived Neurotrophic Factor (BDNF) - Tropomyosin Related Kinase B (TrkB) Signaling Pathway.Journal of Natural Products, vol. 85, no. 3, Mar. 2022, pp. 562–71. Epmc, doi:10.1021/acs.jnatprod.1c01001.
Mehrotra S, Pierce ML, Cao Z, Jabba SV, Gerwick WH, Murray TF. Antillatoxin-Stimulated Neurite Outgrowth Involves the Brain-Derived Neurotrophic Factor (BDNF) - Tropomyosin Related Kinase B (TrkB) Signaling Pathway. Journal of natural products. 2022 Mar;85(3):562–571.
Journal cover image

Published In

Journal of natural products

DOI

EISSN

1520-6025

ISSN

0163-3864

Publication Date

March 2022

Volume

85

Issue

3

Start / End Page

562 / 571

Related Subject Headings

  • Tropomyosin
  • Signal Transduction
  • Receptors, N-Methyl-D-Aspartate
  • Peptides, Cyclic
  • Neuronal Outgrowth
  • Medicinal & Biomolecular Chemistry
  • Lipopeptides
  • Brain-Derived Neurotrophic Factor
  • 4208 Traditional, complementary and integrative medicine
  • 11 Medical and Health Sciences