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热休克蛋白 70 可改善睡眠剥夺引起的小鼠焦虑样行为和认知功能障碍。

Hsp70 ameliorates sleep deprivation-induced anxiety-like behavior and cognitive impairment in mice.

机构信息

Department of Anesthesiology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou 350001, Fujian, China; Department of Anesthesiology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, Fujian, China.

Department of Anesthesiology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, Fujian, China.

出版信息

Brain Res Bull. 2023 Nov;204:110791. doi: 10.1016/j.brainresbull.2023.110791. Epub 2023 Oct 17.

Abstract

BACKGROUND

Many neurobehavioral processes, including psychomotor, cognitive, and affection are negatively impacted by sleep deprivation (SD), which may be harmful to a person's physical and mental health. Heat shock proteins (Hsps) have been demonstrated to play a protective role in a number of neurodegenerative diseases and are essential for maintaining intracellular protein homeostasis, but their roles in SD remain elusive.

METHODS

A mouse SD model was constructed using a modified multi-platform water environment method. The cognitive function was tested by novel object recognition test and Y-maze test, and anxiety-like behaviors were assessed by open field test (OFT). Protein expression was determined by Western blotting assay and ELISA assay.

RESULTS

We found that SD could profoundly enhance anxiety levels and impair cognitive function in mice. SD also reduced the expression levels of p-cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) and increased microglial activation and neuroinflammatory response in the hippocampus of mice. The intranasal injection of human recombinant Hsp70 protein could alleviate SD-induced anxiety and cognitive impairment, as well as restore pCREB and BDNF levels and reduce microglia-induced neuroinflammation in the hippocampus of SD mice.

CONCLUSIONS

Hsp70 treatment might serve as a potential treatment for mitigating SD-related unfavorable symptoms.

摘要

背景

许多神经行为过程,包括精神运动、认知和情感,都会受到睡眠剥夺(SD)的负面影响,这可能对一个人的身心健康有害。热休克蛋白(Hsps)已被证明在许多神经退行性疾病中发挥保护作用,对于维持细胞内蛋白质的稳态至关重要,但它们在 SD 中的作用仍不清楚。

方法

使用改良的多平台水环境方法构建了小鼠 SD 模型。通过新物体识别试验和 Y 迷宫试验测试认知功能,通过旷场试验(OFT)评估焦虑样行为。通过 Western blot 检测和 ELISA 检测蛋白表达。

结果

我们发现 SD 可显著增强小鼠的焦虑水平并损害其认知功能。SD 还降低了 p-CREB 和脑源性神经营养因子(BDNF)的表达水平,并增加了小鼠海马区小胶质细胞的激活和神经炎症反应。人重组 Hsp70 蛋白的鼻内注射可减轻 SD 引起的焦虑和认知障碍,并恢复 pCREB 和 BDNF 水平,减少 SD 小鼠海马区小胶质细胞引起的神经炎症。

结论

Hsp70 治疗可能是减轻 SD 相关不良症状的一种潜在治疗方法。

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