Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Disease

Norah A. Althobaiti*, Farid Menaa*, Aishah E. Albalawi, Johnathan J. Dalzell, Neil D. Warnock, Erin M. Mccammick, Abdulellah Alsolais, Abeer M. Alkhaibari, Brian D. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Background: Whole transgenic or non-transgenic organism model systems allow the screening of pharmacological compounds for protective actions in Alzheimer’s disease (AD). Aim: In this study, a plant parasitic nematode, Globodera pallida, which assimilates intact peptides from the external environment, was investigated as a new potential non-transgenic model system of AD. Methods: Fresh second-stage juveniles of G. pallida were used to measure their chemosensory, perform immunocytochemistry on their neurological structures, evaluate their survival rate, measure reactive oxygen species, and determine total oxidized glutathione to reduced glutathione ratio (GSSG/GSH) levels, before and after treatment with 100 µM of various amyloid beta (Aβ) peptides (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16). Wild-type N2 C. elegans (strain N2) was cultured on Nematode Growth Medium and directly used, as control, for chemosensory assays. Results: We demonstrated that: (i) G. pallida (unlike Caenorhabditis elegans) assimilates amyloid-β (Aβ) peptides which co-localise with its neurological structures; (ii) pre-treatment with various Aβ isoforms (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16) impairs G. pallida’s chemotaxis to differing extents; (iii) Aβ peptides reduced survival, increased the production of ROS, and increased GSSG/GSH levels in this model; (iv) this unique model can distinguish differences between different treatment concentrations, durations, and modalities, displaying good sensitivity; (v) clinically approved neuroprotective agents were effective in protecting G. pallida from Aβ (1–42) exposure. Taken together, the data indicate that G. pallida is an interesting in vivo model with strong potential for discovery of novel bioactive compounds with anti-AD activity.
Original languageEnglish
Article number2481
JournalCells
Volume10
Issue number9
Early online date19 Sep 2021
DOIs
Publication statusEarly online date - 19 Sep 2021

Keywords

  • Alzheimer’s disease
  • amyloid-β
  • Globodera pallida
  • Caenorhabditis elegans
  • oxidative stress
  • in vivo model

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