ArticleMolecular pain2016
Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.
Article in Molecular pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Aberrant stromal tissue factor localisation and mycolactone-driven vascular dysfunction, exacerbated by IL-1β, are linked to fibrin formation in Buruli ulcer lesions.PLoS pathogens · 2022Trial
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- Usefulness of the measurement of neurite outgrowth of primary sensory neurons to study cancer-related painful complications.Biochemical pharmacology · 2021Article
- Pharmacologic management ofExpert review of clinical pharmacology · 2020Review
- Neuronal Regulation of Cutaneous Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2020Review
- Review
- Molecular Informatics Studies of the Iron-Dependent Regulator (ideR) Reveal Potential Novel Anti-Molecules (Basel, Switzerland) · 2019Article
- Human Dorsal Root Ganglia.Frontiers in cellular neuroscience · 2019Review
- The effects of neuregulin-1β on intrafusal muscle fiber formation in neuromuscular coculture of dorsal root ganglion explants and skeletal muscle cells.Skeletal muscle · 2018Article
- Macrophage angiotensin II type 2 receptor triggers neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Angiotensin II Triggers Peripheral Macrophage-to-Sensory Neuron Redox Crosstalk to Elicit Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Buruli Ulcer, a Prototype for Ecosystem-Related Infection, Caused by Mycobacterium ulcerans.Clinical microbiology reviews · 2018Review
- Mycolactone displays anti-inflammatory effects on the nervous system.PLoS neglected tropical diseases · 2017Article
- A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.Toxins · 2017Article
- The chemistry and biology of mycolactones.Beilstein journal of organic chemistry · 2017Review
- The role of urea in neuronal degeneration and sensitization: An in vitro model of uremic neuropathy.Molecular painArticle
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone.
resultsMorphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401.
conclusionMycolactone induces toxic effects in DRG neurons, leading to impaired nociceptor function, neurite degeneration, and cell death, resembling the cutaneous hypoalgesia and nerve damage in individuals with M. Ulcerans infection.
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