Anthelmintic resistance and homeostatic plasticity (Brugia malayi)

Abstract Homeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been exp...

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Autores principales:	Sudhanva S. Kashyap, Saurabh Verma, Mark McHugh, Mengisteab Wolday, Paul D. Williams, Alan P. Robertson, Richard J. Martin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71dc7ab49cf84c24bf93c846c440a3b3
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spelling	oai:doaj.org-article:71dc7ab49cf84c24bf93c846c440a3b32021-12-02T16:08:09ZAnthelmintic resistance and homeostatic plasticity (Brugia malayi)10.1038/s41598-021-93911-42045-2322https://doaj.org/article/71dc7ab49cf84c24bf93c846c440a3b32021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93911-4https://doaj.org/toc/2045-2322Abstract Homeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been explored in parasitic nematodes when treated with therapeutic drugs. Here we have studied the adaptation of Brugia malayi to exposure to the anthelmintic, levamisole that activates muscle AChR ion-channels. We found three phases of the Brugia malayi motility responses as they adapted to levamisole: an initial spastic paralysis; a flaccid paralysis that follows; and finally, a recovery of motility with loss of sensitivity to levamisole at 4 h. Motility, calcium-imaging, patch-clamp and molecular experiments showed the muscle AChRs are dynamic with mechanisms that adjust their subtype composition and sensitivity to levamisole. This homeostatic plasticity allows the parasite to adapt resisting the anthelmintic.Sudhanva S. KashyapSaurabh VermaMark McHughMengisteab WoldayPaul D. WilliamsAlan P. RobertsonRichard J. MartinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sudhanva S. Kashyap Saurabh Verma Mark McHugh Mengisteab Wolday Paul D. Williams Alan P. Robertson Richard J. Martin Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
description	Abstract Homeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been explored in parasitic nematodes when treated with therapeutic drugs. Here we have studied the adaptation of Brugia malayi to exposure to the anthelmintic, levamisole that activates muscle AChR ion-channels. We found three phases of the Brugia malayi motility responses as they adapted to levamisole: an initial spastic paralysis; a flaccid paralysis that follows; and finally, a recovery of motility with loss of sensitivity to levamisole at 4 h. Motility, calcium-imaging, patch-clamp and molecular experiments showed the muscle AChRs are dynamic with mechanisms that adjust their subtype composition and sensitivity to levamisole. This homeostatic plasticity allows the parasite to adapt resisting the anthelmintic.
format	article
author	Sudhanva S. Kashyap Saurabh Verma Mark McHugh Mengisteab Wolday Paul D. Williams Alan P. Robertson Richard J. Martin
author_facet	Sudhanva S. Kashyap Saurabh Verma Mark McHugh Mengisteab Wolday Paul D. Williams Alan P. Robertson Richard J. Martin
author_sort	Sudhanva S. Kashyap
title	Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_short	Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_full	Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_fullStr	Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_full_unstemmed	Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
title_sort	anthelmintic resistance and homeostatic plasticity (brugia malayi)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/71dc7ab49cf84c24bf93c846c440a3b3
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Anthelmintic resistance and homeostatic plasticity (Brugia malayi)

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