Departments of Molecular Pharmacology and Neurosciences, Albert Einstein College of Medicine, NY, USA.
The Neuro- Lab, School of Health and Health Technology, Federal University of Technology, Akure, Nigeria.
Neurotoxicology. 2020 Sep;80:71-75. doi: 10.1016/j.neuro.2020.06.013. Epub 2020 Jul 1.
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。金属暴露与神经毒性和脑损伤有很大关系。此外，晚期糖基化终产物受体（RAGE）也与神经紊乱有关，特别是那些葡萄糖代谢改变的神经紊乱。在这里，我们研究了金属暴露和 RAGE 表达对秀丽隐杆线虫多巴胺（DA）和血清素（SER）神经元的潜在复合效应。此外，我们还评估了 RAGE 表达在高血糖条件下对 DA 和 SER 神经元的影响。用绿色荧光蛋白（GFP）标记新生成的表达 RAGE 的秀丽隐杆线虫在 DA 能和 SER 能神经元中，用镉（Cd）或锰（Mn）处理。此外，还将表达 RAGE 的线虫暴露于高葡萄糖条件下。结果表明，金属在存在和不存在 RAGE 表达的情况下都诱导神经退行性变，但 Cd 和 Mn 处理的线虫之间的退行性变方式不同。此外，表达 RAGE 的线虫在 DA 能和 SER 能神经元中都表现出明显的神经退行性变。我们的结果表明，金属暴露和 RAGE 表达的共同发生会诱导神经退行性变。此外，我们还表明，RAGE 表达会加剧高血糖引起的神经退行性变。
