电针通过抑制自噬相关的铁下垂改善高脂肪饮食/链脲霉素诱导的2型糖尿病小鼠的认知功能。

IF 2.2 4区 农林科学 Q1 VETERINARY SCIENCES
Experimental Animals Pub Date : 2025-04-20 Epub Date: 2024-12-06 DOI:10.1538/expanim.24-0072
Jingzhi Wang, Zhongyu Huang, Yiwen Li, Qian Li, Xi Li, Li Chen
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引用次数: 0

摘要

目前,对于糖尿病相关的认知障碍缺乏明确的药物干预或治疗方法。在此,我们深入研究了电针对高脂肪饮食/链脲霉素(HFD/STZ)诱导的T2DM小鼠认知功能的影响及其机制。western blot检测海马胰岛素抵抗。采用Morris水迷宫测验评估认知功能。采用苏木精伊红染色和尼氏染色观察海马神经元形态。western blot检测突触可塑性。采用免疫荧光、免疫组织化学、western blot和real-time PCR检测大鼠铁下垂标志物、自噬标志物和netrin-1水平。电针治疗可改善T2DM小鼠的空间学习、记忆功能、海马胰岛素抵抗、神经元损伤和突触可塑性。此外,它通过上调GPX4和SLC7A11表达,降低4-HNE表达,有效抑制海马内神经元铁下垂。同时,电针干预可提高T2DM小鼠海马Beclin1和LC3II/LC3I水平,降低p62和磷酸化mTOR水平,提示电针通过抑制mTOR活性促进自噬激活。3- ma介导的自噬抑制破坏了电针对T2DM小鼠神经元铁下垂和认知缺陷的有益作用。此外,电针对自噬和铁下垂的有益作用是通过上调海马中的netrin-1来实现的。我们的研究表明,电针疗法通过激活自噬来抑制神经元铁下垂,从而改善T2DM小鼠的认知缺陷。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Electroacupuncture improves cognitive function in high-fat diet/streptozocin-induced type 2 diabetic mice by inhibiting autophagy-related ferroptosis.

At present, there lacks a definitive pharmaceutical intervention or therapeutic approach for diabetes-associated cognitive impairment. Herein, we delved into the impact of electroacupuncture on cognitive function in high-fat diet/streptozocin (HFD/STZ)-induced type 2 diabetes mellitus (T2DM) mice and underlying mechanisms. Hippocampal insulin resistance was determined by western blot analysis. Cognitive function was evaluated by Morris water maze test. The morphology of the hippocampal neurons was observed through hematoxylin & eosin staining and Nissl staining. Synaptic plasticity was assessed by western blot analysis. Immunofluorescence, immunohistochemistry, western blot and real-time PCR were employed to detect the levels of ferroptosis markers, autophagy markers, and netrin-1. Electroacupuncture treatment exhibited ameliorative outcomes on hippocampal insulin resistance, spatial learning, memory function, neuronal damage, and synaptic plasticity in T2DM mice. Furthermore, it effectively suppressed neuronal ferroptosis in the hippocampus by upregulating GPX4 and SLC7A11 expression, and reducing 4-HNE expression. Meanwhile, electroacupuncture intervention increased the levels of Beclin1 and LC3II/LC3I, as well as decreased the levels of p62 and phosphorylated-mTOR in the hippocampus of T2DM mice, suggesting that electroacupuncture facilitated autophagy activation by inhibiting mTOR activity. 3-MA-mediated autophagy inhibition undermined the beneficial effects of electroacupuncture on neuronal ferroptosis and cognitive deficits in T2DM mice. Additionally, the beneficial effects of electroacupuncture on autophagy and ferroptosis was achieved by upregulation of netrin-1 in the hippocampus. Our study revealed that electroacupuncture therapy inhibited neuronal ferroptosis via the activation of autophagy, thereby ameliorating cognitive deficits in T2DM mice.

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来源期刊
Experimental Animals
Experimental Animals 生物-动物学
CiteScore
2.80
自引率
4.20%
发文量
2
审稿时长
3 months
期刊介绍: The aim of this international journal is to accelerate progress in laboratory animal experimentation and disseminate relevant information in related areas through publication of peer reviewed Original papers and Review articles. The journal covers basic to applied biomedical research centering around use of experimental animals and also covers topics related to experimental animals such as technology, management, and animal welfare.
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