Sericin improves memory and sociability impairments evoked by transient global cerebral ischemia through suppression of hippocampal oxidative stress, inflammation, and apoptosis.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Seyed Mehdi Vatandoust, Javad Mahmoudi, Shahrbanoo Oryan, Fereshteh Farajdokht, Saeed Sadigh-Eteghad, Siamak Sandoghchian Shotorbani, Huaxi Xu, Delaram Eslimi Esfahani
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引用次数: 0

Abstract

Sericin (Ser) is a natural neuroactive macromolecule with diverse pharmacological properties, and our previous findings have shown its neuroprotective potentials. This study aimed to investigate the therapeutic potential of Ser on cognitive dysfunction induced by transient global cerebral ischemia/reperfusion (tGI/R) and its mechanism of action. The tGI/R was induced in BALB/c mice by bilateral occlusion of the common carotid arteries for two 5 min followed by a 10-min reperfusion period. After 24 h, mice were treated with normal saline or different doses of Ser (100, 200, and 300 mg/kg) for 10 days. Cognitive performances were assessed using the Barnes maze and social interaction tasks. Oxidative stress markers including superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA) as well as pro-inflammatory cytokines (interleukin (IL)-6 and tumor necrosis factor-alpha) and anti-inflammatory cytokine (IL-10) were assessed in the hippocampus. Markers of apoptosis (pro- and cleaved caspase-9 and 3, Bax, and Bcl-2) were assessed by Western blotting. Besides, transferase-mediated dUTP nick end-labeling assay was used to detect apoptotic cell death. We show here that Ser administration improved tGI/R-induced cognitive deficits, enhanced the activity of SOD and GPx, increased TAC levels, while reduced MDA levels. Notably, Ser decreased neuronal apoptotic cell death in the hippocampal dentate gyrus (DG) region, accompanied by suppression of neuroinflammation, downregulation of pro-apoptotic proteins (caspase-9, caspases-3, and Bax), and upregulation of anti-apoptotic protein, Bcl-2. Taken together, Ser administration protected hippocampal neurons from apoptotic cell death by impeding oxidative stress and inflammatory responses and, in turn, improved cognitive function in the tGI/R mice.

丝氨酸通过抑制海马氧化应激、炎症和细胞凋亡,改善短暂性全脑缺血引起的记忆和社交障碍。
丝氨酸(Ser)是一种具有多种药理性质的天然神经活性大分子,我们先前的研究结果表明其具有神经保护潜力。本研究旨在探讨Ser对短暂性全脑缺血/再灌注(tGI/R)诱导的认知功能障碍的治疗潜力及其作用机制。在BALB/c小鼠中,通过双侧颈总动脉闭塞两个5分钟,然后再灌注10分钟来诱导tGI/R。24小时后,用生理盐水或不同剂量的Ser(100、200和300mg/kg)处理小鼠10天。认知表现使用巴恩斯迷宫和社交任务进行评估。在海马中评估氧化应激标记物,包括超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、总抗氧化能力(TAC)和丙二醛(MDA),以及促炎细胞因子(白细胞介素(IL)-6和肿瘤坏死因子-α)和抗炎细胞因子(IL-10)。通过蛋白质印迹评估细胞凋亡标记物(前和裂解的胱天蛋白酶-9和3、Bax和Bcl-2)。此外,转移酶介导的dUTP缺口末端标记法用于检测细胞凋亡。我们在这里表明,Ser给药改善了tGI/R诱导的认知缺陷,增强了SOD和GPx的活性,增加了TAC水平,同时降低了MDA水平。值得注意的是,Ser降低了海马齿状回(DG)区域的神经元凋亡细胞死亡,同时抑制了神经炎症,下调了促凋亡蛋白(胱天蛋白酶-9、胱天蛋白酶-3和Bax),上调了抗凋亡蛋白Bcl-2。总之,Ser给药通过阻止氧化应激和炎症反应来保护海马神经元免受细胞凋亡的影响,进而改善tGI/R小鼠的认知功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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