Environmental and occupational metal exposure poses serious global concerns. Metal exposure have severally been associated with neurotoxicity and brain damage. Furthermore, receptor for advanced glycation end products (RAGE) is also implicated in neurological disorders, particularly those with altered glucose metabolism. Here, we examine potential compounding effect of metal exposure and RAGE expression on dopamine (DA) and serotonin (SER) neurons in C. elegans. In addition, we evaluate the effect of RAGE expression on DA and SER neurons in hyperglycemic conditions. Newly generated RAGE-expressing C. elegans tagged with green fluorescent proteins (GFP) in DAergic and SERergic neurons were treated with cadmium (Cd) or manganese (Mn). Additionally, the RAGE-expressing worms were also exposed to high glucose conditions. Results showed metals induced neurodegeneration both in the presence and absence of RAGE expression, but the manner of degeneration differed between Cd and Mn treated nematodes. Furthermore, RAGE-expressing worms showed significant neurodegeneration in both DAergic and SERergic neurons. Our results indicate co-occurrence of metal exposure and RAGE expression can induce neurodegeneration. Additionally, we show that RAGE expression can exacerbate hyperglycemic induced neurodegeneration.

环境和职业金属暴露引起了严重的全球关注。金属接触分别与神经毒性和脑损伤有关。此外，晚期糖基化终产物 (RAGE) 受体也与神经系统疾病有关，尤其是那些葡萄糖代谢改变的疾病。在这里，我们研究了金属暴露和 RAGE 表达对秀丽隐杆线虫中多巴胺 (DA) 和血清素 (SER) 神经元的潜在复合效应。此外，我们评估了 RAGE 表达对高血糖条件下 DA 和 SER 神经元的影响。新生成的表达 RAGE 的线虫用镉 (Cd) 或锰 (Mn) 处理 DAergic 和 SERergic 神经元中用绿色荧光蛋白 (GFP) 标记的细胞。此外，表达 RAGE 的蠕虫也暴露于高葡萄糖条件下。结果表明，在 RAGE 表达存在和不存在的情况下，金属都会诱导神经变性，但在 Cd 和 Mn 处理的线虫之间，变性方式不同。此外，表达 RAGE 的蠕虫在 DAergic 和 SERergic 神经元中均表现出显着的神经变性。我们的结果表明金属暴露和 RAGE 表达的同时发生可以诱导神经变性。此外，我们表明 RAGE 表达可以加剧高血糖诱导的神经变性。