Xi'an Key Laboratory of Pathogenic Microorganism and Tumor Immunity, Xi'an Medical University, Xi'an, 710021, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Xi'an Medical University, Xi'an, 710021, China.
Neurotox Res. 2023 Dec;41(6):627-637. doi: 10.1007/s12640-023-00677-w. Epub 2023 Nov 16.
Dysfunction in the cholinergic system and oxidative stress are closely related and play roles in Alzheimer's disease (AD). Scopolamine (Scop), which is commonly used to induce cholinergic system damage in cells and animals, also evokes oxidative stress. Our previous study indicated that the peptide (m) RVD-hemopressin (RVD) reversed the memory-impairing effect of Scop in mice by activating cannabinoid receptor 1 (CBR1), but the mechanism was unclear. In this study, we found that RVD inhibited the oxidative stress, apoptosis, decreased cell viability and downregulation of synapse-associated proteins induced by Scop in HT22 cells. The effect was associated with the BDNF/TrkB/Akt pathway, and the effects of RVD outlined above could be blocked by an antagonist of CBR1. These results suggest that RVD may be a potential drug candidate for disorders associated with damage to the cholinergic system and oxidative stress, such as AD.
胆碱能系统功能障碍与氧化应激密切相关，在阿尔茨海默病（AD）中发挥作用。东莨菪碱（Scop）常用于诱导细胞和动物的胆碱能系统损伤，也会引发氧化应激。我们之前的研究表明，肽（m）RVD-hemopressin（RVD）通过激活大麻素受体 1（CBR1）逆转了 Scop 对小鼠的记忆损伤作用，但机制尚不清楚。在这项研究中，我们发现 RVD 抑制了 Scop 诱导的 HT22 细胞中的氧化应激、细胞凋亡、细胞活力降低和突触相关蛋白下调。该作用与 BDNF/TrkB/Akt 通路有关，CBR1 的拮抗剂可阻断 RVD 的上述作用。这些结果表明，RVD 可能是一种有潜力的候选药物，可用于治疗与胆碱能系统损伤和氧化应激相关的疾病，如 AD。
