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HT-ac 和 HBET 通过 PKA-CREB-BDNF 通路维持线粒体功能,从而提高热应激小鼠的认知和学习能力。

The combination of HT-ac and HBET improves the cognitive and learning abilities of heat-stressed mice by maintaining mitochondrial function through the PKA-CREB-BDNF pathway.

机构信息

Department of Nutrition and Food Hygiene, Faculty of Naval Medicine, Naval Medical University, No. 800 Xiangyin Road, Shanghai 200433, China.

出版信息

Food Funct. 2022 Jun 6;13(11):6166-6179. doi: 10.1039/d1fo04157f.

DOI:10.1039/d1fo04157f
PMID:35582986
Abstract

The aim was to investigate whether the combination of hydroxytyrosol acetate (HT-ac) and ethyl β-hydroxybutyrate (HBET) can improve the cognition of heat-stressed mice, meanwhile exploring the mechanism of action. Mice were divided into 5 groups: control, heat-stressed, HT-ac, HBET, and HT-ac + HBET. Mice were gavaged for 21 days and exposed to heat (42.5 ± 0.5 °C, RH 60 ± 10%, 1 h day) on days 15-21, except for the control group. Results showed that the combination of HT-ac + HBET improved the cognitive and learning abilities of heat-stressed mice, which were tested by Morris water maze, shuttle box, and jumping stage tests. The combination of HT-ac + HBET maintained the integrity of neurons and mitochondria of heat-stressed mice. Likewise, this combination increased the mitochondrial membrane potential, the ATP content, the expression of phosphorylated PKA, BDNF, phosphorylated CREB and Bcl-2, and decreased the expression of Bax, caspase-3, and intracytoplasmic Cyt in heat-stressed mice.

摘要

目的是研究羟基酪醇乙酸酯(HT-ac)和β-羟基丁酸乙酯(HBET)的联合使用是否可以改善热应激小鼠的认知能力,并探讨其作用机制。将小鼠分为 5 组:对照组、热应激组、HT-ac 组、HBET 组和 HT-ac+HBET 组。除对照组外,所有组别的小鼠在第 15-21 天连续灌胃 21 天,并接受热应激(42.5±0.5°C,相对湿度 60±10%,1 小时/天)。结果表明,HT-ac+HBET 联合使用可改善热应激小鼠的认知和学习能力,通过 Morris 水迷宫、穿梭箱和跳台试验进行测试。该联合用药还可维持热应激小鼠神经元和线粒体的完整性。同样,该联合用药可提高线粒体膜电位、ATP 含量、磷酸化 PKA、BDNF、磷酸化 CREB 和 Bcl-2 的表达水平,降低热应激小鼠细胞浆 Cyt 中 Bax、caspase-3 的表达。

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