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绿茶儿茶素对转基因A53T小鼠模型帕金森病症状发展的治疗潜力。

Therapeutic potential of green tea catechins on the development of Parkinson's disease symptoms in a transgenic A53T mouse model.

作者信息

Riegelman Elizabeth, Xue Kathy, Wang Jia-Sheng, Tang Lili

机构信息

Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, USA.

出版信息

Nutr Neurosci. 2025 Jul;28(7):863-879. doi: 10.1080/1028415X.2024.2427753. Epub 2024 Nov 29.

Abstract

This study aimed to evaluate the effects of green tea catechins on the prevention of Parkinson's disease neurobehavioral symptoms and α-synuclein blood plasma concentration in a hemizygous transgenic A53T mouse model. Thirty 6-month-old male mice were randomly assigned to three groups ( = 10/group): control, low-dose, and high-dose, receiving green tea polyphenol (GTP) treatment in their drinking water at 0%, 0.5%, and 1.5%, respectively, over a 90-day period. The efficacy of dosing was assessed by analyzing the bioaccumulation of tea catechins in urine samples collected from metabolic cages on days 0, 30, 60, and 90, using LC/Q-TOF analysis. PD-related behavioral impairments were measured with open field and rotarod performance tests on days 0, 45, and 90. On day 90, plasma α-synuclein levels were analyzed via enzyme-linked immunosorbent assay (ELISA) to assess treatment effects. Circulating tea catechin metabolites were detected in treated groups by day 30, with levels progressively increasing through day 90. By day 90, control mice exhibited significant deficits in rotarod performance, while both low- and high-dose groups maintained or improved their maximum time on the rotarod. Open field testing indicated reduced anxiety-related behavior in control mice compared to treated groups. ELISA analysis revealed significantly lower circulating α-synuclein levels in high-dose mice compared to controls. Our findings indicate that sustained administration of tea catechins significantly reduces circulating α-synuclein levels in blood plasma, improves motor coordination in a dose-dependent manner, and modulates anxiety-related behaviors in a PD mouse model.

摘要

本研究旨在评估绿茶儿茶素对半合子转基因A53T小鼠模型帕金森病神经行为症状预防及α-突触核蛋白血浆浓度的影响。30只6月龄雄性小鼠随机分为三组(每组n = 10):对照组、低剂量组和高剂量组,在90天内分别给予其含0%、0.5%和1.5%绿茶多酚(GTP)的饮用水。通过使用液相色谱/四极杆飞行时间质谱(LC/Q-TOF)分析,对第0、30、60和90天从代谢笼收集的尿液样本中茶儿茶素的生物蓄积进行分析,以评估给药效果。在第0、45和90天,通过旷场试验和转棒试验测量与帕金森病相关的行为障碍。在第90天,通过酶联免疫吸附测定(ELISA)分析血浆α-突触核蛋白水平,以评估治疗效果。到第30天,在治疗组中检测到循环茶儿茶素代谢物,其水平在第90天逐渐升高。到第90天,对照组小鼠在转棒试验中的表现出现显著缺陷,而低剂量组和高剂量组在转棒试验中的最长时间保持不变或有所改善。旷场试验表明,与治疗组相比,对照组小鼠与焦虑相关的行为减少。ELISA分析显示,与对照组相比,高剂量组小鼠循环α-突触核蛋白水平显著降低。我们的研究结果表明,在帕金森病小鼠模型中,持续给予茶儿茶素可显著降低血浆中循环α-突触核蛋白水平,以剂量依赖方式改善运动协调性,并调节与焦虑相关的行为。

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