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

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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.

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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

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  1. Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, 1300 Morris Park Avenue, Forchheimer Building, Room 209, Bronx, NY, 10461, USA

    Adi Pinkas, Kun He Lee, Pan Chen & Michael Aschner

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  1. Adi Pinkas
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  2. Kun He Lee
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  3. Pan Chen
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Correspondence to Adi Pinkas.

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Grant Support for This Research

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

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Pinkas, A., Lee, K.H., Chen, P. et al. A C. elegans Model for the Study of RAGE-Related Neurodegeneration. Neurotox Res 35, 19–28 (2019). https://doi.org/10.1007/s12640-018-9918-y

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