槲皮素减轻铝纳米颗粒诱导的神经毒性:记忆、海马完整性和MAPK信号的体视学和分子研究。

IF 4.9 3区 生物学 Q1 BIOLOGY
EXCLI Journal Pub Date : 2025-07-02 eCollection Date: 2025-01-01 DOI:10.17179/excli2025-8315
Zahra Esmaili, Mohammad Shabani, Fatemeh Karimi, Moazamehosadat Razavinasab, Meysam Ahmadi-Zeidabadi, Majid Reza Farokhi, Maryam Moosavi
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引用次数: 0

摘要

新出现的证据表明铝(Al)暴露与阿尔茨海默病(AD)的发展之间有很强的联系。由于其纳米级尺寸和增加的表面积,纳米铝(ALNP)比大块铝表现出更大的神经毒性,引起了人们对其在神经退行性疾病中的作用的关注。虽然槲皮素已被认为具有神经保护作用,但其对抗alnp诱导的海马神经变性和MAPK信号失调的能力在很大程度上仍未被探索。本研究调查了槲皮素在雄性瑞士小鼠中改善alnp诱导的记忆缺陷、海马体参数改变以及caspase-3和MAPK信号中断的潜力。小鼠(SWR/J, 8-10周龄)接受ALNP (10 mg/kg,腹腔注射10天)加槲皮素或不加槲皮素,剂量分别为1、10或100 mg/kg(口服)。记忆表现通过升高+迷宫(EPM)、新物体识别(NOR)和y迷宫任务进行评估,随后对海马进行体视学和western blot分析。研究结果表明,槲皮素(100 mg/kg)可显著保护海马体积和齿状回(DG)和杏仁核1 (CA1)神经元的完整性,这是参与记忆加工和输出信号的关键区域。此外,槲皮素通过增强ERK磷酸化调节MAPK信号,同时抑制alnp诱导的p38和裂解caspase-3的激活,提示槲皮素在减少神经炎症和细胞凋亡中的作用。这是第一个证明槲皮素可以抵消ALNP的神经毒性作用的研究,突出了它作为治疗纳米颗粒诱导的阿尔茨海默病样模型神经变性的治疗策略的潜力。另见图解摘要。1).
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Quercetin mitigates aluminum nanoparticle-induced neurotoxicity: a stereological and molecular study on memory, hippocampal integrity, and MAPK signaling.

Quercetin mitigates aluminum nanoparticle-induced neurotoxicity: a stereological and molecular study on memory, hippocampal integrity, and MAPK signaling.

Quercetin mitigates aluminum nanoparticle-induced neurotoxicity: a stereological and molecular study on memory, hippocampal integrity, and MAPK signaling.

Quercetin mitigates aluminum nanoparticle-induced neurotoxicity: a stereological and molecular study on memory, hippocampal integrity, and MAPK signaling.

Emerging evidence suggests a strong association between aluminum (Al) exposure and the development of Alzheimer's disease (AD). Due to their nanoscale size and increased surface area, Al nanoparticles (ALNP) exhibit greater neurotoxicity than bulk Al, raising concerns about their role in neurodegenerative disorders. While quercetin has been recognized for its neuroprotective effects, its ability to counteract ALNP-induced hippocampal neurodegeneration and dysregulated MAPK signaling remains largely unexplored. This study investigated the potential of quercetin to ameliorate ALNP-induced memory deficits, alterations in hippocampal stereological parameters, and disruptions in caspase-3 and MAPK signaling in male Swiss mice. Mice (SWR/J, aged 8-10 weeks) received ALNP (10 mg/kg, intraperitoneally for 10 days) with or without quercetin at doses of 1, 10, or 100 mg/kg (orally). Memory performance was assessed using the elevated plus maze (EPM), novel object recognition (NOR), and Y-maze tasks, followed by stereological and western blot analyses of the hippocampus. Our findings revealed that quercetin (100 mg/kg) significantly preserved hippocampal volume and neuronal integrity in the dentate gyrus (DG) and Cornu Ammonis 1 (CA1)-key regions involved in memory processing and output signaling. Additionally, quercetin modulated MAPK signaling by enhancing ERK phosphorylation while suppressing ALNP-induced activation of p38 and cleaved caspase-3, suggesting a role in reducing neuroinflammation and apoptosis. This is the first study to demonstrate that quercetin can counteract the neurotoxic effects of ALNP, highlighting its potential as a therapeutic strategy against nanoparticle-induced neurodegeneration in an Alzheimer's-like model. See also the graphical abstract.(Fig. 1).

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来源期刊
EXCLI Journal
EXCLI Journal BIOLOGY-
CiteScore
8.00
自引率
2.20%
发文量
65
审稿时长
6-12 weeks
期刊介绍: EXCLI Journal publishes original research reports, authoritative reviews and case reports of experimental and clinical sciences. The journal is particularly keen to keep a broad view of science and technology, and therefore welcomes papers which bridge disciplines and may not suit the narrow specialism of other journals. Although the general emphasis is on biological sciences, studies from the following fields are explicitly encouraged (alphabetical order): aging research, behavioral sciences, biochemistry, cell biology, chemistry including analytical chemistry, clinical and preclinical studies, drug development, environmental health, ergonomics, forensic medicine, genetics, hepatology and gastroenterology, immunology, neurosciences, occupational medicine, oncology and cancer research, pharmacology, proteomics, psychiatric research, psychology, systems biology, toxicology
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