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Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling

Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host...

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Autores principales: de Lange, Anja, Prodjinotho, Ulrich Fabien, Tomes, Hayley, Hagen, Jana, Jacobs, Brittany-Amber, Smith, Katherine, Horsnell, William, Sikasunge, Chummy, Hockman, Dorit, Selkirk, Murray E., Prazeres da Costa, Clarissa, Raimondo, Joseph Valentino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785214/
https://www.ncbi.nlm.nih.gov/pubmed/33347447
http://dx.doi.org/10.1371/journal.pntd.0008966
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author de Lange, Anja
Prodjinotho, Ulrich Fabien
Tomes, Hayley
Hagen, Jana
Jacobs, Brittany-Amber
Smith, Katherine
Horsnell, William
Sikasunge, Chummy
Hockman, Dorit
Selkirk, Murray E.
Prazeres da Costa, Clarissa
Raimondo, Joseph Valentino
author_facet de Lange, Anja
Prodjinotho, Ulrich Fabien
Tomes, Hayley
Hagen, Jana
Jacobs, Brittany-Amber
Smith, Katherine
Horsnell, William
Sikasunge, Chummy
Hockman, Dorit
Selkirk, Murray E.
Prazeres da Costa, Clarissa
Raimondo, Joseph Valentino
author_sort de Lange, Anja
collection PubMed
description Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis.
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spelling pubmed-77852142021-01-13 Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling de Lange, Anja Prodjinotho, Ulrich Fabien Tomes, Hayley Hagen, Jana Jacobs, Brittany-Amber Smith, Katherine Horsnell, William Sikasunge, Chummy Hockman, Dorit Selkirk, Murray E. Prazeres da Costa, Clarissa Raimondo, Joseph Valentino PLoS Negl Trop Dis Research Article Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis. Public Library of Science 2020-12-21 /pmc/articles/PMC7785214/ /pubmed/33347447 http://dx.doi.org/10.1371/journal.pntd.0008966 Text en © 2020 de Lange et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
de Lange, Anja
Prodjinotho, Ulrich Fabien
Tomes, Hayley
Hagen, Jana
Jacobs, Brittany-Amber
Smith, Katherine
Horsnell, William
Sikasunge, Chummy
Hockman, Dorit
Selkirk, Murray E.
Prazeres da Costa, Clarissa
Raimondo, Joseph Valentino
Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling
title Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling
title_full Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling
title_fullStr Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling
title_full_unstemmed Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling
title_short Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling
title_sort taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785214/
https://www.ncbi.nlm.nih.gov/pubmed/33347447
http://dx.doi.org/10.1371/journal.pntd.0008966
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