Abstract
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.
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Funding
This work is supported by Youth Innovation Team Project funded by Shaanxi Provincial Education Department (21JP112), the Students' Innovation Training Program in Shaanxi Province (S202111840034), the Students' Innovation Training Program in Xi’an Medical University (121522099) and National Natural Science Foundation of China (82103189).
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Ruisan Zhang and Peng Chen wrote the main manuscript text and prepared Fig. 7. Xinliang He and Jianghong Cheng prepared Figs. 1–3. Xiaofan Zhang, Chen Han and Yifan Liu prepared Figs. 4–6. Yang Wang and Ruisan Zhang designed the experimental scheme.
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Zhang, R., He, X., Cheng, J. et al. (m) RVD-hemopressin (α) Ameliorated Oxidative Stress, Apoptosis and Damage to the BDNF/TrkB/Akt Pathway Induced by Scopolamine in HT22 Cells. Neurotox Res 41, 627–637 (2023). https://doi.org/10.1007/s12640-023-00677-w
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DOI: https://doi.org/10.1007/s12640-023-00677-w