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Neurotoxicity Research

, Volume 35, Issue 1, pp 19–28 | Cite as

A C. elegans Model for the Study of RAGE-Related Neurodegeneration

  • Adi PinkasEmail author
  • Kun He Lee
  • Pan Chen
  • Michael Aschner
ORIGINAL ARTICLE

Abstract

The receptor for advanced glycation products (RAGE) is a cell surface, multi-ligand receptor belonging to the immunoglobulin superfamily; this receptor is implicated in a variety of maladies, via inflammatory pathways and induction of oxidative stress. Currently, RAGE is being studied using a limited number of mammalian in vivo, and some complementary in vitro, models. Here, we present a Caenorhabditis elegans model for the study of RAGE-related pathology: a transgenic strain, expressing RAGE in all neurons, was generated and subsequently tested behaviorally, developmentally, and morphologically. In addition to RAGE expression being associated with a significantly shorter lifespan, the following behavioral observations were made when RAGE-expressing worms were compared to the wild type: RAGE-expressing worms showed an impaired dopaminergic system, evaluated by measuring the fluorescent signal of GFP tagging; these worms exhibited decreased locomotion—both general and following ethanol exposure—as measured by counting body bends in adult worms; RAGE expression was also associated with impaired recovery of quiescence and pharyngeal pumping secondary to heat shock, as a significantly smaller fraction of RAGE-expressing worms engaged in these behaviors in the 2 h immediately following the heat shock. Finally, significant developmental differences were also found between the two strains: RAGE expression leads to a significantly smaller fraction of hatched eggs 24 h after laying and also to a significantly slower developmental speed overall. As evidence for the role of RAGE in a variety of neuropathologies accumulates, the use of this novel and expedient model should facilitate the elucidation of relevant underlying mechanisms and also the development of efficient therapeutic strategies.

Keywords

RAGE C. elegans Behavior Neurodegeneration Development 

Abbreviations

RAGE

Receptor for advanced glycation end products

HMGB1

High-mobility group box 1

LPA

Lysophosphatidic acid

AD

Alzheimer’s disease

PD

Parkinson’s disease

HD

Huntington’s disease

CJD

Creutzfeldt-Jakob’s disease

ALS

Amyotrophic lateral sclerosis

Notes

Compliance with Ethical Standards

Grant Support for This Research

This research was supported by NIEHS—R01 ES07331, R01 ES10563, and R01 ES020852.

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Authors and Affiliations

  1. 1.Albert Einstein College of MedicineJack and Pearl Resnick CampusBronxUSA

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