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脑室内注射β-淀粉样蛋白1-42对补充牛磺酸的老年大鼠认知功能的影响及此过程中过氧化物酶体蛋白的变化。

The effect of intracerebroventricular amyloid beta 1-42 application on cognitive functions in aged rats supplemented with taurine and the change of peroxisomal proteins in this process.

作者信息

Aslan Karakelle Nida, Dinçer Sibel, Yar Sağlam Atiye Seda

机构信息

Department of Physiology, Lokman Hekim University Faculty of Medicine, Ankara, Turkey.

Department of Physiology, Gazi University Faculty of Medicine, Ankara, Turkey.

出版信息

Brain Res Bull. 2021 Jul;172:89-97. doi: 10.1016/j.brainresbull.2021.04.011. Epub 2021 Apr 20.

DOI:10.1016/j.brainresbull.2021.04.011
PMID:33892084
Abstract

OBJECTIVE

The aim of our study is to investigate the change of peroxisomal proteins in the neurodegenerative and oxidative process caused by the neurotoxicity of Aβ 1-42 in aged rats supplemented with taurine and to show the possible positive effects of taurine in this process.

METHODS

30 Wistar albino rats were randomly divided into 5 groups as control, sham, Aβ 1-42, taurine, and Aβ 1-42+taurine. Taurine administration continued for 6 weeks (1000 mg/kg/day with drinking water). Stereotaxic surgery was applied to all groups (intracerebroventricular per lateral ventricle needle only or 5 μl, PBS, or Aβ 1-42). Spatial learning and memory performances of the animals were evaluated with Morris water maze and elevated plus maze. The levels of MDA and GSH were measured as oxidative stress parameters in the cerebral cortex and hippocampus. Expressions of CAT, PEX14, PMP70 of peroxisomal membrane proteins were indicated by Western blot analysis.

RESULTS

Our results showed that injection of Aβ 1-42 decreased the spatial learning and memory performance, cortex CAT and hippocampus PEX14, PMP70 and GSH levels, and increased cortex and hippocampus MDA levels (p < 0.05). Although the administration of taurine partially ameliorated the adverse effects of Aβ 1-42 injection, a significant difference was found only at the hippocampus GSH levels (p < 0.05). Also, taurine caused anxiety at this dose (p < 0.05).

DISCUSSION

In conclusion, decreased peroxisomal proteins and antioxidant capacity in neurodegenerative and oxidative processes induced by intracerebroventricular Aβ 1-42 injection showed that peroxisomes may play a role in this process and taurine supplementation may have positive effects especially in increasing antioxidant capacity.

摘要

目的

本研究旨在探讨补充牛磺酸的老年大鼠在Aβ 1-42神经毒性所致神经退行性变和氧化过程中过氧化物酶体蛋白的变化,并揭示牛磺酸在此过程中可能的积极作用。

方法

将30只Wistar白化大鼠随机分为5组,即对照组、假手术组、Aβ 1-42组、牛磺酸组和Aβ 1-42+牛磺酸组。牛磺酸给药持续6周(通过饮用水给予,剂量为1000 mg/kg/天)。对所有组进行立体定向手术(仅在侧脑室每侧脑室注射针或注射5 μl PBS或Aβ 1-42)。用Morris水迷宫和高架十字迷宫评估动物的空间学习和记忆能力。测定大脑皮质和海马中丙二醛(MDA)和谷胱甘肽(GSH)的水平作为氧化应激参数。通过蛋白质印迹分析检测过氧化物酶体膜蛋白过氧化氢酶(CAT)、过氧化物酶体生物合成蛋白14(PEX14)、过氧化物酶体膜蛋白70(PMP70)的表达。

结果

我们的结果表明,注射Aβ 1-42降低了空间学习和记忆能力、大脑皮质CAT以及海马PEX14、PMP70和GSH水平,并增加了大脑皮质和海马MDA水平(p < 0.05)。虽然给予牛磺酸部分改善了注射Aβ 1-42的不良反应,但仅在海马GSH水平上发现有显著差异(p < 0.05)。此外,此剂量的牛磺酸引起了焦虑(p < 0.05)。

讨论

总之,脑室内注射Aβ 1-42诱导的神经退行性变和氧化过程中过氧化物酶体蛋白和抗氧化能力的降低表明,过氧化物酶体可能在此过程中起作用,补充牛磺酸可能尤其在提高抗氧化能力方面具有积极作用。

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