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

作     者：Pinkas, Adi Lee, Kun He Chen, Pan Aschner, Michael 

作者机构：Albert Einstein Coll Med Jack & Pearl Resnick Campus1300 Morris Pk Ave Bronx NY 10461 USA 

出 版 物：《NEUROTOXICITY RESEARCH》 (神经毒性研究)

年 卷 期：2019年第35卷第1期

页      面：19-28页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NIEHS-R01 ES07331 R01 ES10563 R01 ES020852 

主　　题：RAGE C elegans Behavior Neurodegeneration Development 

摘      要：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 locomotionboth general and following ethanol exposureas 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 2h 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 24h 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.