High-intensity interval training reduces Tau and beta-amyloid accumulation by improving lactate-dependent mitophagy in rats with type 2 diabetes.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/ijbms.2024.77038.16664
Pouria Khosravi, Fereshte Shahidi, Arezoo Eskandari, Kayvan Khoramipour
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Abstract

Objectives: This study aimed to investigate the effect of 8-week high-intensity interval training (HIIT) on lactate-induced mitophagy in the hippocampus of rats with type 2 diabetes.

Materials and methods: 28 Wistar male rats were divided into four groups randomly: (i) control (Co), (ii) exercise (EX), (iii) type 2 diabetes (T2D), and (iv) type 2 diabetes + exercise (T2D + Ex). The rats in the T2D and T2D + Ex groups were fed a high-fat diet for two months, then a single dose of STZ (35 mg/kg) was injected to induce diabetes. The EX and T2D + Ex groups performed 4-10 intervals of treadmill running at 80-100% of Vmax. Serum and hippocampal levels of lactate, as well as hippocampal levels of monocarboxylate transporter2 (MCT2), sirtuin1 (SIRT1), forkhead box protein O (FOXO3), light chain 3 (LC3), PTEN-induced kinase 1 (PINK1), parkin, beta-amyloid (Aβ), hyperphosphorylated tau protein (TAU), Malondialdehyde (MDA), and antioxidant enzymes were measured. One-way ANOVA and Tukey post-hoc tests were used to analyze the data.

Results: Serum and hippocampal levels of lactate as well as hippocampal levels of MCT2, SIRT1, FOXO3, LC3, PINK1, Parkin, and antioxidant enzymes were higher while hippocampal levels of Aβ, TAU, and MDA were lower in T2D+EX compared to T2D group (P-value<0.05).

Conclusion: HIIT could improve mitophagy through Lactate-SIRT1-FOXO3-PINK1/Parkin signaling in the hippocampus of rats with T2D reducing the accumulation of Tau and Aβ, which may reduce the risk of memory impairments.

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高强度间歇训练通过改善2型糖尿病大鼠的乳酸依赖性有丝分裂,减少Tau和β-淀粉样蛋白的积累。
研究目的材料与方法:将28只Wistar雄性大鼠随机分为四组:①对照组(Co);②运动组(EX);③2型糖尿病组(T2D);④2型糖尿病+运动组(T2D + Ex)。T2D组和T2D + Ex组大鼠以高脂肪饮食喂养两个月,然后注射单剂量STZ(35毫克/千克)诱发糖尿病。EX组和T2D + Ex组在80-100% Vmax的速度下进行4-10个间隔的跑步机跑步。血清和海马中的乳酸水平,以及海马中的单羧酸盐转运体2(MCT2)、sirtuin1(SIRT1)、叉头盒蛋白O(FOXO3)、轻链3(LC3)和胰岛素(EX)的水平、对单羧酸盐转运体2(MCT2)、sirtuin1(SIRT1)、叉头盒蛋白O(FOXO3)、轻链3(LC3)、PTEN诱导激酶1(PINK1)、parkin、β-淀粉样蛋白(Aβ)、高磷酸化tau蛋白(TAU)、丙二醛(MDA)和抗氧化酶进行了测定。采用单因素方差分析和Tukey事后检验分析数据:结果:与T2D组相比,T2D+EX组血清和海马体乳酸水平以及海马体MCT2、SIRT1、FOXO3、LC3、PINK1、Parkin和抗氧化酶水平较高,而海马体Aβ、TAU和MDA水平较低(P-value):HIIT可通过乳酸-SIRT1-FOXO3-PINK1/Parkin信号转导改善T2D大鼠海马的有丝分裂,减少Tau和Aβ的积累,从而降低记忆损伤的风险。
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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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