Kasselman Lora J, Renna Heather A, Voloshyna Iryna, Pinkhasov Aaron, Gomolin Irving H, Teboul Isaac, De Leon Joshua, Carsons Steven E, Reiss Allison B
NYU Long Island School of Medicine, Foundations of Medicine, Mineola, NY, USA.
NYU Winthrop Hospital, Winthrop Research Institute, Department of Medicine, Mineola, NY, USA.
J Tradit Complement Med. 2022 Feb 1;12(5):447-454. doi: 10.1016/j.jtcme.2022.01.006. eCollection 2022 Sep.
Resveratrol is a bioactive molecule used in dietary supplements and herbal medicines and consumed worldwide. Prior work showed that resveratrol's anti-atherogenic properties are mediated in part through the adenosine A2A receptor. The present study explores the potential contribution of adenosine A2A receptor activation to neuroprotective action of resveratrol on cognitive deficits in a model of atherosclerosis-prone systemic lupus erythematosus.
Using behavioral analysis (open field, static rod, novel object recognition) and QRT-PCR, this study measured working memory, anxiety, motor coordination, and expression of mRNA in the brain.
Data indicate that resveratrol increases working memory, on average but not statistically, and shows a trend towards improved motor coordination (p = 0.07) in atherosclerosis-prone lupus mice. Additionally, resveratrol tends to increase mRNA levels of SIRT1, decrease vascular endothelial growth factor and CX3CL1 mRNA in the hippocampus. Istradefylline, an adenosine A2A receptor antagonist, antagonizes the effects of resveratrol on working memory (p = 0.04) and the expression of SIRT1 (p = 0.03), vascular endothelial growth factor (p = 0.04), and CX3CL1 (p = 0.03) in the hippocampus.This study demonstrates that resveratrol could potentially be a therapeutic candidate in the modulation of cognitive dysfunction in neuropsychiatric lupus, especially motor incoordination. Further human studies, as well as optimization of resveratrol administration, could confirm whether resveratrol may be an additional resource available to reduce the burden of cognitive impairment associated with lupus. Additionally, further studies need to address the role of A2A blockade in cognitive function among the autoimmune population.
autoimmunity, inflammation, neurology.
白藜芦醇是一种生物活性分子，用于膳食补充剂和草药中，在全球范围内都有消费。先前的研究表明，白藜芦醇的抗动脉粥样硬化特性部分是通过腺苷A2A受体介导的。本研究探讨了腺苷A2A受体激活对易患动脉粥样硬化的系统性红斑狼疮模型中白藜芦醇对认知缺陷的神经保护作用的潜在贡献。
本研究使用行为分析（旷场试验、静态杆试验、新物体识别试验）和定量逆转录聚合酶链反应（QRT-PCR），测量了工作记忆、焦虑、运动协调性以及大脑中mRNA的表达。
数据表明，在易患动脉粥样硬化的狼疮小鼠中，白藜芦醇平均增加了工作记忆，但无统计学意义，并且显示出运动协调性改善的趋势（p = 0.07）。此外，白藜芦醇倾向于增加海马体中SIRT1的mRNA水平，降低血管内皮生长因子和CX3CL1的mRNA水平。腺苷A2A受体拮抗剂异丁司特拮抗了白藜芦醇对工作记忆（p = 0.04）以及海马体中SIRT1（p = 0.03）、血管内皮生长因子（p = 0.04）和CX3CL1（p = 0.03）表达的影响。本研究表明，白藜芦醇可能是调节神经精神性狼疮认知功能障碍，尤其是运动不协调的潜在治疗候选药物。进一步的人体研究以及白藜芦醇给药方式的优化，可以证实白藜芦醇是否可能是减轻狼疮相关认知障碍负担的额外资源。此外，需要进一步研究来探讨A2A受体阻断在自身免疫人群认知功能中的作用。
EVISE分类法：自身免疫、炎症、神经学。
