Publications

BibTex format

@article{Anand:2016:10.1177/1744806916654144,
author = {Anand, U and Sinisi, M and Fox, M and MacQuillan, A and Quick, T and Korchev, Y and Bountra, C and McCarthy, T and Anand, P},
doi = {10.1177/1744806916654144},
journal = {Molecular Pain},
title = {Mycolactone mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: mechanisms underlying hypoalgesia in Buruli Ulcer},
url = {http://dx.doi.org/10.1177/1744806916654144},
volume = {12},
year = {2016}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Mycolactone (ML) is a polyketide toxin secreted by the mycobacterium M.ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients withBuruli Ulcer. A recent pre-clinical study proposed that ML may produce analgesia via activationof the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shownanalgesic efficacy in animal models and clinical trials for neuropathic pain. We thereforeinvestigated the morphological and functional effects of ML in cultured human and rat dorsal rootganglia (DRG) neurons, and the role of AT2R using EMA401. Primary sensory neurons wereprepared from avulsed cervical human DRG, and rat DRG. 24 hours after plating, neurons wereincubated for 24 to 96 hours with synthetic ML A/B, followed by immunostaining with antibodiesto PGP9.5, Gap43,  tubulin, or Mitotracker dye staining. Acute functional effects wereexamined by measuring capsaicin responses with calcium imaging in DRG neuronal culturestreated with ML.Results: Morphological effects: ML treated cultures showed dramatically reduced numbers ofsurviving neurons and non-neuronal cells, reduced Gap43 and  tubulin expression, degeneratingneurites and reduced cell body diameter, compared with controls. Dose related reduction ofneurite length was observed in ML treated cultures. Mitochondria were distributed throughout thelength of neurites and soma of control neurons, but clustered in the neurites and soma of MLtreated neurons. Functional effects: ML treated human and rat DRG neurons showed doserelated inhibition of capsaicin responses, which were reversed by calcineurin inhibitorcyclosporine and phosphodiesterase inhibitor IBMX, indicating involvement of cAMP/ATPreduction. The morphological and functional effects of ML were not altered by Angiotensin II orAT2R antagonist EMA401.3Conclusion: ML induces toxic effects in DRG neurons, leading to impaired nociceptor function,neurite degeneration and cell death, resembling the cuta
AU  - Anand,U
AU  - Sinisi,M
AU  - Fox,M
AU  - MacQuillan,A
AU  - Quick,T
AU  - Korchev,Y
AU  - Bountra,C
AU  - McCarthy,T
AU  - Anand,P
DO  - 10.1177/1744806916654144
PY  - 2016///
SN  - 1744-8069
TI  - Mycolactone mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: mechanisms underlying hypoalgesia in Buruli Ulcer
T2  - Molecular Pain
UR  - http://dx.doi.org/10.1177/1744806916654144
UR  - http://hdl.handle.net/10044/1/32884
VL  - 12
ER  -

Download

ProfessorPraveenAnand

Contact

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)