白藜芦醇对tau突变腺病毒诱导的阿尔茨海默病模型小鼠认知功能障碍的改善作用及其机制研究
Study on the improvement effect and mechanism of resveratrol on cognitive impairment in tau mutant adenovirus-induced alzheimer's disease model mice.
摘要(中文译文)
Tau蛋白过度磷酸化和神经炎症在阿尔茨海默病（AD）的发生和进展中发挥重要作用。SIRT1已被认为参与突触可塑性、认知功能和记忆的调控，并与自噬及炎症相关信号通路（包括AMPK/mTOR/ULK1和NF-κB）的调节有关。据报道，白藜芦醇（RSV）可改善AD模型中的认知障碍，但主要是在Aβ相关病理背景下；然而，其在Tau驱动病理中的潜在效应及 underlying 机制仍不完全清楚。旨在探讨RSV对Tau突变诱导的阿尔茨海默病小鼠认知障碍的影响，并探索其对自噬和神经炎症的作用。采用AAV-P301L-Tau建立Tau病变模型。通过行为学测试评估认知功能；使用HE和Nissl染色评估海马损伤，同时通过免疫荧光染色评估自噬。采用Western blot、qRT-PCR和CCK-8实验检测机制。RSV治疗与AD小鼠神经元损伤减轻、p-Tau积累减少及认知障碍改善相关。在体外也观察到一致的趋势，即在AAV-P301L-Tau诱导的BV2细胞中，RSV治疗与细胞活力增加及自噬相关标志物的调节相关。此外，RSV给药伴随SIRT1、AMPK/mTOR/ULK1和NF-κB通路相关信号组分的协同变化，同时炎症介质表达降低。RSV治疗与AMPK/mTOR/ULK1和NF-κB通路相关信号组分的协同调节以及AD小鼠认知表现的改善相关。这些发现支持RSV在Tau驱动的神经退行性病理中具有潜在的治疗相关性，但仍需进一步研究以阐明其 underlying 机制。
Abstract
Tau protein hyperphosphorylation and neuroinflammation playimportant roles in the onset and progression of Alzheimer's disease (AD). SIRT1has been implicated in the regulation of synaptic plasticity, cognitive function, andmemory, and is associated with the modulation of autophagy-and inflammation-related signaling pathways, including AMPK/mTOR/ULK1 and NF-κB. Resveratrol(RSV) has been reported to ameliorate cognitive impairment in AD models,primarily in the context of Aβ-related pathology; however, its potential effects andunderlying mechanisms in Tau-driven pathology remain incompletely understood. To investigate the effect of RSV on cognitive impairment in mice withTau mutation-induced Alzheimer's disease, and to explore its effects on autophagyand neuroinflammation. Tauopathy models were established using AAV-P301L-Tau. Cognitivefunction was assessed via behavioral tests; Hippocampal injury was evaluatedAccepted manuscriptACCEPTED MANUSCRIPTusing HE and Nissl staining, while autophagy was assessed byimmunofluorescence staining. Mechanisms were examined using Western blot,qRT-PCR, and CCK-8 assays. RSV treatment was associated with attenuation of neuronal damage,reduction of p-Tau accumulation, and improvement of cognitive impairment in ADmice. Consistent trends were observed in vitro, where RSV treatment wasassociated with increased cell viability and modulation of autophagy-relatedmarkers in AAV-P301L-Tau-induced BV2 cells. In addition, RSV administration wasaccompanied by coordinated changes in signaling components related to SIRT1,AMPK/mTOR/ULK1, and NF-κB pathways, along with reduced expression ofinflammatory mediators. RSV treatment was associated with coordinated modulation ofsignaling components related to the AMPK/mTOR/ULK1 and NF-κB pathways,together with improvements in cognitive performance in AD mice. These findingssupport the potential therapeutic relevance of RSV in Tau-drivenneurodegenerative pathology, while further studies are required to clarify theunderlying mechanisms.
如何引用
AMA
Shuting Chen, Kexuan Zhao, Zhidan Shi, Chu Zhang, Hao Wu, Meng Tian, et al. Study on the improvement effect and mechanism of resveratrol on cognitive impairment in tau mutant adenovirus-induced alzheimer's disease model mice.. Psychopharmacology. 2026; doi:10.1007/s00213-026-07048-1.
APA
Shuting Chen, Kexuan Zhao, Zhidan Shi, Chu Zhang, Hao Wu, Meng Tian, et al (2026). Study on the improvement effect and mechanism of resveratrol on cognitive impairment in tau mutant adenovirus-induced alzheimer's disease model mice.. Psychopharmacology. https://doi.org/10.1007/s00213-026-07048-1
GB/T 7714
Shuting Chen, Kexuan Zhao, Zhidan Shi, Chu Zhang, Hao Wu, Meng Tian, et al. Study on the improvement effect and mechanism of resveratrol on cognitive impairment in tau mutant adenovirus-induced alzheimer's disease model mice.[J]. Psychopharmacology, 2026 doi:10.1007/s00213-026-07048-1.
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