Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response

T. Sinnige, P. Ciryam, S. Casford, C.M. Dobson, M. de Bono, M. Vendruscolo, PLOS ONE 14 (2019) e0217746.

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Journal Article | Published | English
Author
Sinnige, Tessa; Ciryam, Prashanth; Casford, Samuel; Dobson, Christopher M.; de Bono, MarioIST Austria ; Vendruscolo, Michele
Abstract
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 CO2, compared to controls. Ca2+ 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.
Publishing Year
Date Published
2019-05-31
Journal Title
PLOS ONE
Volume
14
Issue
5
Article Number
e0217746
ISSN
IST-REx-ID

Cite this

Sinnige T, Ciryam P, Casford S, Dobson CM, de Bono M, Vendruscolo M. Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response. PLOS ONE. 2019;14(5):e0217746. doi:10.1371/journal.pone.0217746
Sinnige, T., Ciryam, P., Casford, S., Dobson, C. M., de Bono, M., & Vendruscolo, M. (2019). Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response. PLOS ONE, 14(5), e0217746. https://doi.org/10.1371/journal.pone.0217746
Sinnige, Tessa, Prashanth Ciryam, Samuel Casford, Christopher M. Dobson, Mario de Bono, and Michele Vendruscolo. “Expression of the Amyloid-β Peptide in a Single Pair of C. Elegans Sensory Neurons Modulates the Associated Behavioural Response.” PLOS ONE 14, no. 5 (2019): e0217746. https://doi.org/10.1371/journal.pone.0217746.
T. Sinnige, P. Ciryam, S. Casford, C. M. Dobson, M. de Bono, and M. Vendruscolo, “Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response,” PLOS ONE, vol. 14, no. 5, p. e0217746, 2019.
Sinnige T, Ciryam P, Casford S, Dobson CM, de Bono M, Vendruscolo M. 2019. Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response. PLOS ONE. 14(5), e0217746.
Sinnige, Tessa, et al. “Expression of the Amyloid-β Peptide in a Single Pair of C. Elegans Sensory Neurons Modulates the Associated Behavioural Response.” PLOS ONE, vol. 14, no. 5, Public Library of Science, 2019, p. e0217746, doi:10.1371/journal.pone.0217746.

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