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Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response
Although the aggregation of the amyloid-β peptide (Aβ) into amyloid fibrils is a well-established hallmark of Alzheimer’s disease, the complex mechanisms linking this process to neurodegeneration are still incompletely understood. The nematode worm C. elegans is a valuable model organism through whi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544271/ https://www.ncbi.nlm.nih.gov/pubmed/31150491 http://dx.doi.org/10.1371/journal.pone.0217746 |
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author | Sinnige, Tessa Ciryam, Prashanth Casford, Samuel Dobson, Christopher M. de Bono, Mario Vendruscolo, Michele |
author_facet | Sinnige, Tessa Ciryam, Prashanth Casford, Samuel Dobson, Christopher M. de Bono, Mario Vendruscolo, Michele |
author_sort | Sinnige, Tessa |
collection | PubMed |
description | Although the aggregation of the amyloid-β peptide (Aβ) into amyloid fibrils is a well-established hallmark of Alzheimer’s disease, the complex mechanisms linking this process to neurodegeneration are still incompletely understood. The nematode worm C. elegans is a valuable model organism through which to study these mechanisms because of its simple nervous system and its relatively short lifespan. Standard Aβ-based C. elegans models of Alzheimer’s disease are designed to study the toxic effects of the overexpression of Aβ in the muscle or nervous systems. However, the wide variety of effects associated with the tissue-level overexpression of Aβ makes it difficult to single out and study specific cellular mechanisms related to the onset of Alzheimer’s disease. Here, to better understand how to investigate the early events affecting neuronal signalling, we created a C. elegans model expressing Aβ42, the 42-residue form of Aβ, from a single-copy gene insertion in just one pair of glutamatergic sensory neurons, the BAG neurons. In behavioural assays, we found that the Aβ42-expressing animals displayed a subtle modulation of the response to CO(2), compared to controls. Ca(2+) imaging revealed that the BAG neurons in young Aβ42-expressing nematodes were activated more strongly than in control animals, and that neuronal activation remained intact until old age. Taken together, our results suggest that Aβ42-expression in this very subtle model of AD is sufficient to modulate the behavioural response but not strong enough to generate significant neurotoxicity, suggesting that slightly more aggressive perturbations will enable effectively studies of the links between the modulation of a physiological response and its associated neurotoxicity. |
format | Online Article Text |
id | pubmed-6544271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-65442712019-06-17 Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response Sinnige, Tessa Ciryam, Prashanth Casford, Samuel Dobson, Christopher M. de Bono, Mario Vendruscolo, Michele PLoS One Research Article Although the aggregation of the amyloid-β peptide (Aβ) into amyloid fibrils is a well-established hallmark of Alzheimer’s disease, the complex mechanisms linking this process to neurodegeneration are still incompletely understood. The nematode worm C. elegans is a valuable model organism through which to study these mechanisms because of its simple nervous system and its relatively short lifespan. Standard Aβ-based C. elegans models of Alzheimer’s disease are designed to study the toxic effects of the overexpression of Aβ in the muscle or nervous systems. However, the wide variety of effects associated with the tissue-level overexpression of Aβ makes it difficult to single out and study specific cellular mechanisms related to the onset of Alzheimer’s disease. Here, to better understand how to investigate the early events affecting neuronal signalling, we created a C. elegans model expressing Aβ42, the 42-residue form of Aβ, from a single-copy gene insertion in just one pair of glutamatergic sensory neurons, the BAG neurons. In behavioural assays, we found that the Aβ42-expressing animals displayed a subtle modulation of the response to CO(2), compared to controls. Ca(2+) imaging revealed that the BAG neurons in young Aβ42-expressing nematodes were activated more strongly than in control animals, and that neuronal activation remained intact until old age. Taken together, our results suggest that Aβ42-expression in this very subtle model of AD is sufficient to modulate the behavioural response but not strong enough to generate significant neurotoxicity, suggesting that slightly more aggressive perturbations will enable effectively studies of the links between the modulation of a physiological response and its associated neurotoxicity. Public Library of Science 2019-05-31 /pmc/articles/PMC6544271/ /pubmed/31150491 http://dx.doi.org/10.1371/journal.pone.0217746 Text en © 2019 Sinnige 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 Sinnige, Tessa Ciryam, Prashanth Casford, Samuel Dobson, Christopher M. de Bono, Mario Vendruscolo, Michele Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response |
title | Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response |
title_full | Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response |
title_fullStr | Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response |
title_full_unstemmed | Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response |
title_short | Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response |
title_sort | expression of the amyloid-β peptide in a single pair of c. elegans sensory neurons modulates the associated behavioural response |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544271/ https://www.ncbi.nlm.nih.gov/pubmed/31150491 http://dx.doi.org/10.1371/journal.pone.0217746 |
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