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

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Cells
• Subjects: Alzheimer’s disease; amyloid-β; <i>Globodera pallida</i>; <i>Caenorhabditis elegans</i>; oxidative stress; in vivo model
• Online Access: https://www.mdpi.com/2073-4409/10/9/2481

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, <i>Globodera pallida</i>, which assimilates intact peptides from the external environment, was investigated as a new potential non-transgenic model system of AD. <i>Methods:</i> Fresh second-stage juveniles of <i>G. pallida</i> 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 <i>C. elegans</i> (strain N2) was cultured on Nematode Growth Medium and directly used, as control, for chemosensory assays. Results: We demonstrated that: (i) <i>G. pallida</i> (unlike <i>Caenorhabditis elegans</i>) 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 <i>G. pallida</i>’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 <i>G. pallida</i> from Aβ (1–42) exposure. Taken together, the data indicate that <i>G. pallida</i> is an interesting in vivo model with strong potential for discovery of novel bioactive compounds with anti-AD activity.