Antillatoxin-Stimulated Neurite Outgrowth Involves the Brain-Derived Neurotrophic Factor (BDNF) - Tropomyosin Related Kinase B (TrkB) Signaling Pathway.
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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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
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
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