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

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

Research output: Contribution to journalArticle

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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.

LanguageEnglish (US)
Pages1-10
Number of pages10
JournalNeurotoxicity Research
DOIs
StateAccepted/In press - Jun 4 2018

Fingerprint

Shock
Hot Temperature
Caenorhabditis elegans
Locomotion
Eggs
Immunoglobulins
Oxidative Stress
Oxidative stress
Ethanol
Pathology
Ligands
Neurons
Recovery
Therapeutics
Neuropathology
In Vitro Techniques
Behavior Observation Techniques

Keywords

  • Behavior
  • C. elegans
  • Development
  • Neurodegeneration
  • RAGE

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

A C. elegans Model for the Study of RAGE-Related Neurodegeneration. / Pinkas, Adi; Lee, Kun He; Chen, Pan; Aschner, Michael.

In: Neurotoxicity Research, 04.06.2018, p. 1-10.

Research output: Contribution to journalArticle

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