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牛磺酸,一种必需氨基酸,通过抑制α-突触核蛋白聚集和增加多巴胺释放来减轻鱼藤酮诱导的大鼠帕金森病。

Taurine, an essential amino acid, attenuates rotenone-induced Parkinson's disease in rats by inhibiting alpha-synuclein aggregation and augmenting dopamine release.

作者信息

Onuelu Jackson E, Ben-Azu Benneth, Adebayo Olusegun G, Fokoua Aliance R, Nekabari Miracle K, Ozah Esther O, Iwhiwhu Prosper, Ajayi Abayomi M, Oyovwi Obukohwo M, Omogbiy Itiviere A, Eduviere Anthony T, Ojezele Matthew O

机构信息

DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, Department of Pharmacology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria.

DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, Department of Pharmacology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria; Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.

出版信息

Behav Brain Res. 2025 Mar 5;480:115397. doi: 10.1016/j.bbr.2024.115397. Epub 2024 Dec 12.

Abstract

Reducing antioxidant levels exacerbates the generation of reactive oxygen/nitrogen species, leading to alpha-synuclein aggregation and the degeneration of dopaminergic neurons. These play a key role in the onset of Parkinson's disease (PD), for which effective treatment remains elusive. This study examined the neuroprotective effects of taurine, an essential β-amino acid with antioxidant and antiinflammation properties, in Swiss male mice exposed to rotenone-induced PD. Mice (20-25 g) were grouped into seven groups (n = 9) and treated with taurine alone (5, 10 and 20 mg/kg, p.o) or levodopa (10 mg/kg, p.o) for 28 consecutive days following intraperitoneal co-administration of rotenone (1.5 mg/kg, in 5 % dimethylsulfoxide) for 14 alternate days. Open-field, rota-rod and hanging-wire motor performance and coordination tests were conducted on days 26-28. Oxidative stress and neuroinflammatory markers; levels of acetylcholinesterase enzyme activity, dopamine, and alpha-synuclein were assayed in the striatal and prefrontal-cortical regions alongside histological examinations. Rotenone significantly reduced latency to fall and akinesia-like behavior with several slip/error relative to vehicle groups. Taurine increased the latency to fall, notably improving motor coordination, locomotor deficit, and neuromuscular competence. Also, rotenone significantly increased malondialdehyde and nitrite; while decreasing acetylcholinesterase activity, glutathione, catalase, superoxide-dismutase, and glutathione-S-transferase levels in the striatum and prefrontal-cortex respectively, which were attenuated by taurine. Taurine increased dopamine levels in the striatum and prefrontal cortex dose-independently. Like carbidopa, taurine decreased alpha-synuclein, tumor-necrosis factor-α and interleukin-6 levels in the striatum and prefrontal-cortex. Additionally, taurine-reversed rotenone-induced neurodegeneration in the striatum and prefrontal cortex indicates neuroprotective function. Conclusively, taurine attenuates rotenone-induced PD-like behavior by enhancing the brain's antioxidant system, inhibiting pro-inflammatory cytokine release, reducing α-synuclein formation, and augmenting dopaminergic release in mice's brains.

摘要

降低抗氧化剂水平会加剧活性氧/氮物种的产生,导致α-突触核蛋白聚集和多巴胺能神经元变性。这些在帕金森病(PD)的发病过程中起关键作用,而针对该病的有效治疗方法仍然难以捉摸。本研究检测了牛磺酸(一种具有抗氧化和抗炎特性的必需β-氨基酸)对暴露于鱼藤酮诱导的帕金森病的瑞士雄性小鼠的神经保护作用。将小鼠(20 - 25克)分为七组(n = 9),在每隔一天腹腔注射鱼藤酮(1.5毫克/千克,溶于5%二甲基亚砜)共14天后,连续28天单独给予牛磺酸(5、10和20毫克/千克,口服)或左旋多巴(10毫克/千克,口服)。在第26 - 28天进行旷场试验、转棒试验和悬线试验以评估运动性能和协调性。检测纹状体和前额叶皮质区域的氧化应激和神经炎症标志物;测定乙酰胆碱酯酶活性、多巴胺和α-突触核蛋白水平,并进行组织学检查。与溶媒对照组相比,鱼藤酮显著缩短了小鼠跌落潜伏期,并出现类似运动不能的行为以及多次滑倒/失误。牛磺酸增加了跌落潜伏期,显著改善了运动协调性、运动缺陷和神经肌肉能力。此外,鱼藤酮显著增加了丙二醛和亚硝酸盐水平;同时分别降低了纹状体和前额叶皮质中的乙酰胆碱酯酶活性、谷胱甘肽、过氧化氢酶、超氧化物歧化酶和谷胱甘肽-S-转移酶水平,而牛磺酸可使其减弱。牛磺酸剂量依赖性地增加了纹状体和前额叶皮质中的多巴胺水平。与卡比多巴一样,牛磺酸降低了纹状体和前额叶皮质中的α-突触核蛋白、肿瘤坏死因子-α和白细胞介素-6水平。此外,牛磺酸逆转了鱼藤酮诱导的纹状体和前额叶皮质神经退行性变,表明其具有神经保护功能。总之,牛磺酸通过增强大脑的抗氧化系统、抑制促炎细胞因子释放、减少α-突触核蛋白形成以及增加小鼠大脑中的多巴胺能释放,减轻了鱼藤酮诱导的帕金森病样行为。

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