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槲皮素对帕金森病大鼠模型运动障碍和焦虑样行为的神经保护作用。

Neuroprotective effects of quercetin on motor impairments and anxiety-like behaviors in a rat model of Parkinson's disease.

作者信息

Yousefi Maryam, Mirshekar Mohammad Ali, Afsharfar Maryam, Arabmoazzen Saeideh, Haghparast Elham

机构信息

Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; Student Research Committee, Zahedan University of Medical Sciences, Zahedan, Iran.

Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan 98167-4318, Iran.

出版信息

Behav Brain Res. 2025 Sep 13;493:115692. doi: 10.1016/j.bbr.2025.115692. Epub 2025 Jun 10.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments such as bradykinesia and rigidity, and non-motor deficits including anxiety. These phenomena are closely associated with underlying pathological processes including oxidative stress(OS) and mitochondrial dysfunction that arise from the degeneration of dopaminergic neurons in the substantia nigra. Recent studies have shown that flavonoids like quercetin have neuroprotective effects through antioxidant and anti-inflammatory properties. In this study, we aimed to evaluate the impact of quercetin on motor function, anxiety-like behaviors, and Interleukin-6 (IL-6) levels in hippocampal dentate gyrus tissue in a rat model of PD induced by 6-hydroxydopamine (6-OHDA) and examine the behavioral findings with the use of two doses (10 and 25 mg/kg) of quercetin. Forty male Wistar rats were divided into five groups: control, sham, Parkinson's, and two quercetin-treated PD groups (10 and 25 mg/kg), and 6-OHDA (8 μg/3 μl) was injected into the left medial forebrain bundle (MFB) in three of them to induce PD. The behavioral assessments evaluated motor function and anxiety-like behaviors, including apomorphine-induced rotation, rotarod, wire hanging, elevated plus maze, and open field tests. Our results indicate that quercetin treatment significantly reduced apomorphine-induced rotations, supporting the results of rotarod and wire hanging tests, improved motor coordination, with the 25 mg/kg dose showing greater efficacy. Quercetin also alleviated anxiety-like behaviors in a dose-dependent manner based on the results of the elevated plus maze and open field tests. In addition, the results showed a significant elevation of IL-6 in the hippocampus of PD rats compared to the control group, and quercetin treatment can reduce its levels, though the levels remained higher than in the sham and control groups. These findings suggest that quercetin ameliorates both motor and anxiety-like deficits in a 6-OHDA rat model of Parkinson's disease, potentially through modulation of hippocampal neuro-inflammation, highlighting its promise as a multi-target therapeutic agent in PD.

摘要

帕金森病(PD)是一种进行性神经退行性疾病,其特征在于运动障碍,如运动迟缓、僵硬,以及非运动缺陷,包括焦虑。这些现象与潜在的病理过程密切相关,包括氧化应激(OS)和线粒体功能障碍,这些病理过程源于黑质中多巴胺能神经元的退化。最近的研究表明,像槲皮素这样的黄酮类化合物具有抗氧化和抗炎特性,从而具有神经保护作用。在本研究中,我们旨在评估槲皮素对6-羟基多巴胺(6-OHDA)诱导的帕金森病大鼠模型的运动功能、焦虑样行为以及海马齿状回组织中白细胞介素-6(IL-6)水平的影响,并使用两种剂量(10和25mg/kg)的槲皮素来检验行为学结果。40只雄性Wistar大鼠被分为五组:对照组、假手术组、帕金森病组以及两个槲皮素治疗的帕金森病组(10和25mg/kg),其中三组大鼠的左侧内侧前脑束(MFB)被注射6-OHDA(8μg/3μl)以诱导帕金森病。行为学评估包括运动功能和焦虑样行为,包括阿扑吗啡诱导的旋转试验、转棒试验、悬线试验、高架十字迷宫试验和旷场试验。我们的结果表明,槲皮素治疗显著减少了阿扑吗啡诱导的旋转次数,这与转棒试验和悬线试验的结果一致,改善了运动协调性,25mg/kg剂量显示出更大的疗效。基于高架十字迷宫试验和旷场试验的结果,槲皮素还以剂量依赖的方式减轻了焦虑样行为。此外,结果显示与对照组相比,帕金森病大鼠海马中的IL-6显著升高,槲皮素治疗可以降低其水平,尽管该水平仍高于假手术组和对照组。这些发现表明,槲皮素可改善6-OHDA诱导的帕金森病大鼠模型中的运动和焦虑样缺陷,可能是通过调节海马神经炎症实现的,这突出了其作为帕金森病多靶点治疗药物的潜力。

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