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探索治疗潜力:阿片肽-13的神经保护作用促进亨廷顿病大鼠模型的持续功能性运动恢复。

Exploring the therapeutic potential: Apelin-13's neuroprotective effects foster sustained functional motor recovery in a rat model of Huntington's disease.

作者信息

Torkamani-Dordshaikh Shaysteh, Darabi Shahram, Norouzian Mohsen, Bahar Reza, Beirami Amirreza, Moghaddam Meysam Hassani, Fathi Mobina, Vakili Kimia, Tahmasebinia Foozhan, Bahrami Maryam, Abbaszadeh Hojjat Allah, Aliaghaei Abbas

机构信息

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Anat Cell Biol. 2024 Sep 30;57(3):419-430. doi: 10.5115/acb.23.284. Epub 2024 Jul 31.

Abstract

Huntington's disease (HD) is a hereditary condition considered by the progressive degeneration of nerve cells in the brain, resultant in motor dysfunction and cognitive impairment. Despite current treatment modalities including pharmaceuticals and various therapies, a definitive cure remains elusive. Therefore, this study investigates the therapeutic potential effect of Apelin-13 in HD management. Thirty male Wistar rats were allocated into three groups: a control group, a group with HD, and a group with both HD and administered Apelin-13. Apelin-13 was administered continuously over a 28-day period at a dosage of around 30 mg/kg to mitigate inflammation in rats subjected to 3-NP injection within an experimental HD model. Behavioral tests, such as rotarod, electromyography (EMG), elevated plus maze, and open field assessments, demonstrated that Apelin-13 improved motor function and coordination in rats injected with 3-NP. Apelin-13 treatment significantly increased neuronal density and decreased glial cell counts compared to the control group. Immunohistochemistry analysis revealed reduced gliosis and expression of inflammatory factors in the treatment group. Moreover, Apelin-13 administration led to elevated levels of glutathione and reduced reactive oxygen species (ROS) level in the treated group. Apelin-13 demonstrates neuroprotective effects, leading to improved movement and reduced inflammatory and fibrotic factors in the HD model.

摘要

亨廷顿病(HD)是一种遗传性疾病,其特征是大脑中的神经细胞进行性退化,导致运动功能障碍和认知障碍。尽管目前有包括药物和各种疗法在内的治疗方式,但仍难以找到确切的治愈方法。因此,本研究调查了Apelin-13在HD治疗中的潜在疗效。将30只雄性Wistar大鼠分为三组:对照组、HD组和HD且给予Apelin-13组。在实验性HD模型中,以约30mg/kg的剂量连续28天给予Apelin-13,以减轻接受3-NP注射的大鼠的炎症。行为测试,如转棒试验、肌电图(EMG)、高架十字迷宫试验和旷场评估,表明Apelin-13改善了注射3-NP的大鼠的运动功能和协调性。与对照组相比,Apelin-13治疗显著增加了神经元密度,减少了神经胶质细胞计数。免疫组织化学分析显示治疗组的神经胶质增生和炎症因子表达减少。此外,给予Apelin-13导致治疗组谷胱甘肽水平升高,活性氧(ROS)水平降低。Apelin-13具有神经保护作用,可改善HD模型中的运动并减少炎症和纤维化因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e719/11424562/4fecce6d9e15/acb-57-3-419-f1.jpg

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