Cyanidin improves spatial memory and cognition in bisphenol A-induced rat model of Alzheimer's-like neuropathology by restoring canonical Wnt signaling

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2024-05-04 DOI:10.1016/j.taap.2024.116953

Swathi Suresh, Chitra Vellapandian

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引用次数: 0

Abstract

Introduction

Research has unveiled the neurotoxicity of Bisphenol A (BPA) linked to neuropathological traits of Alzheimer's disease (AD) through varied mechanisms. This study aims to investigate the neuroprotective properties of cyanidin, an anthocyanin, in an in vivo model of BPA-induced Alzheimer's-like neuropathology.

Methods

Three-week-old Sprague-Dawley rats were randomly assigned to four groups: vehicle control, negative control (BPA exposure), low-dose cyanidin treatment (BPA + cyanidin 5 mg/kg), and high-dose cyanidin treatment (BPA + cyanidin 10 mg/kg). Spatial memory was assessed through behavioral tests, including the Y-maze, novel object recognition, and Morris water maze. After behavioral tests, animals were euthanized, and brain regions were examined for acetylcholinesterase inhibition, p-tau, Wnt3, GSK3β, and β-catenin levels, antioxidant activities, and histopathological changes.

Results

BPA-exposed groups displayed memory impairments, while cyanidin-treated groups showed significant memory improvement (p < 0.0001). Cyanidin down regulated p-tau and glycogen synthase kinase-3β (GSK3β) and restored Wnt3 and β-catenin levels (p < 0.0001). Moreover, cyanidin exhibited antioxidant properties, elevating catalase and superoxide dismutase levels. The intervention significantly reduced the concentrations of acetylcholinesterase in the cortex and hippocampus in comparison to the groups treated with BPA (p < 0.0001). Significant gender-based disparities were not observed.

Conclusion

Cyanidin demonstrated potent neuroprotection against BPA-induced Alzheimer's-like neuropathology by enhancing antioxidant defenses, modulating tau phosphorylation by restoring the Wnt/β-catenin pathway, and ameliorating spatial memory deficits. This study highlights the therapeutic potential of cyanidin in countering neurotoxicity linked to BPA exposure.

Abstract Image

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矢车菊素通过恢复典型的 Wnt 信号传导，改善双酚 A 诱导的阿尔茨海默氏症样神经病理学大鼠模型的空间记忆和认知能力。

导言：研究发现，双酚 A（BPA）的神经毒性与阿尔茨海默病（AD）的神经病理学特征有关，其机制多种多样。本研究旨在探讨花青素（一种花色素）在双酚A诱导的阿尔茨海默氏症样神经病理学体内模型中的神经保护特性：方法：将三周大的 Sprague-Dawley 大鼠随机分为四组：车辆对照组、阴性对照组（双酚 A 暴露）、低剂量青花素处理组（双酚 A + 青花素 5 mg/kg）和高剂量青花素处理组（双酚 A + 青花素 10 mg/kg）。空间记忆通过行为测试进行评估，包括Y迷宫、新物体识别和莫里斯水迷宫。行为测试结束后，对动物实施安乐死，并检测脑区乙酰胆碱酯酶抑制、p-tau、Wnt3、GSK3β和β-catenin水平、抗氧化活性以及组织病理学变化：结果表明：暴露于双酚 A 的组记忆力受损，而青花素处理的组记忆力明显改善（p 结论：青花素对双酚 A 暴露组的记忆力有抑制作用：青花素通过增强抗氧化防御能力、恢复Wnt/β-catenin通路调节tau磷酸化以及改善空间记忆缺陷，对双酚A诱导的阿尔茨海默氏症样神经病理表现出了有效的神经保护作用。这项研究凸显了青花素在对抗与双酚A暴露相关的神经毒性方面的治疗潜力。

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.