Neurobehavioral, biochemical and histological assessment of the effects of resveratrol on cuprizone-induced demyelination in mice: role of autophagy modulation.

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Doaa M Samy, Eiman I Zaki, Passainte S Hassaan, Doaa A Abdelmonsif, Dalia Y Mohamed, Samar R Saleh
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引用次数: 1

Abstract

Resveratrol is known to exhibit neuroprotective effects in many neurological disorders via autophagy modulation. However, controversial results have been reported about the therapeutic potential of resveratrol and the implication of autophagy in demyelinating diseases. This study aimed to evaluate the autophagic changes in cuprizone-intoxicated C57Bl/6 mice and explore the effect of autophagy activation by resveratrol on the demyelination and remyelination processes. Mice were fed with chow containing 0.2% cuprizone for 5 weeks, followed by a cuprizone-free diet for 2 weeks. Resveratrol (250 mg/kg/day) and/or chloroquine (an autophagy inhibitor; 10 mg/kg/day) were given for 5 weeks starting from the third week. At the end of the experiment, animals were tested on rotarod and then sacrificed for biochemical assessment, luxol fast blue (LFB) staining, and transmission electron microscopy (TEM) imaging of the corpus callosum. We observed that cuprizone-induced demyelination was associated with impaired degradation of autophagic cargo, induction of apoptosis, and manifest neurobehavioral disturbances. Oral treatment with resveratrol promoted motor coordination and improved remyelination with regular compacted myelin in most axons without a significant impact on myelin basic protein (MBP) mRNA expression. These effects are mediated, at least in part, via activating autophagic pathways that may involve SIRT1/FoxO1 activation. This study verified that resveratrol dampens cuprizone-induced demyelination, and partially enhances myelin repair through modulation of the autophagic flux, since interruption of the autophagic machinery by chloroquine reversed the therapeutic potential of resveratrol.

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白藜芦醇对铜酮诱导小鼠脱髓鞘影响的神经行为学、生化和组织学评价:自噬调节的作用。
已知白藜芦醇通过自噬调节在许多神经系统疾病中表现出神经保护作用。然而,关于白藜芦醇的治疗潜力和自噬在脱髓鞘疾病中的意义,有争议的结果已经报道。本研究旨在评价铜酮中毒C57Bl/6小鼠的自噬变化,探讨白藜芦醇激活自噬对脱髓鞘和再髓鞘形成过程的影响。小鼠先喂食含0.2%铜酮的食物5周,然后再喂食不含铜酮的食物2周。白藜芦醇(250 mg/kg/天)和/或氯喹(一种自噬抑制剂;10 mg/kg/天),从第3周开始连续5周。实验结束后,处死动物进行生化评价、luxol快蓝(LFB)染色、胼胝体透射电镜(TEM)成像。我们观察到铜酮诱导的脱髓鞘与自噬货物降解受损、诱导细胞凋亡和明显的神经行为障碍有关。口服白藜芦醇可促进运动协调,改善髓鞘再生,大多数轴突有规律的髓鞘致密化,但对髓鞘碱性蛋白(MBP) mRNA表达无显著影响。这些作用至少部分是通过激活自噬途径介导的,自噬途径可能涉及SIRT1/FoxO1的激活。本研究证实,白藜芦醇可以抑制铜酮诱导的脱髓鞘,并通过调节自噬通量部分增强髓磷脂修复,因为氯喹打断自噬机制逆转了白藜芦醇的治疗潜力。
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来源期刊
Journal of physiology and biochemistry
Journal of physiology and biochemistry 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
86
审稿时长
6-12 weeks
期刊介绍: The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.
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