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Neuroprotective effects of magnesium l-threonate in a hypoxic zebrafish model
BMC Neuroscience ( IF 2.4 ) Pub Date : 2020-06-26 , DOI: 10.1186/s12868-020-00580-6
Young-Sung Kim 1 , Young Ju Won 1 , Byung Gun Lim 1 , Too Jae Min 2 , Yeon-Hwa Kim 3 , Il Ok Lee 1
Affiliation  

Hypoxia inhibits the uptake of glutamate (a major neurotransmitter in the brain closely related to cognitive function) into brain cells, and the initial response of cells to cortical hypoxia depends on glutamate. Previous studies have suggested that magnesium may have protective effects against hypoxic injuries. In particular, magnesium l-threonate (MgT) may increase magnesium ion concentrations in the brain better than MgSO4 and improve cognitive function. We evaluated cell viability under hypoxic conditions in the MgT- and MgSO4-treated human SH-SY5Y neurons, in vivo behavior using the T-maze test following hypoxia in MgT-treated zebrafish, activity of brain mitochondrial dehydrogenase by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and protein expression of the excitatory amino acid transporter (EAAT) 4 glutamate transporter by western blotting. Among the groups treated with hypoxia, cell viability significantly increased when pre-treated with 1 or 10 mM MgT (p = 0.009 and 0.026, respectively). Despite hypoxic insult, MgT-treated zebrafish showed preferences for the red compartment (p = 0.025 for distance and p = 0.007 for frequency of entries), suggesting memory preservation. TTC staining showed reduced cerebral infarction and preserved absorbance in the MgT-treated zebrafish brain after hypoxia (p = 0.010 compared to the hypoxia group). In addition, western blot showed upregulation of EAAT4 protein in the MgT treated group. Pre-treatment with MgT attenuated cell death and cerebral infarction due to hypoxia and protected cognitive function in zebrafish. In addition, MgT appeared to modulate expression of the glutamate transporter, EAAT4.

中文翻译:

L-苏糖酸镁对缺氧斑马鱼模型的神经保护作用

缺氧会抑制谷氨酸(大脑中与认知功能密切相关的主要神经递质)进入脑细胞的摄取,细胞对皮质缺氧的初始反应依赖于谷氨酸。先前的研究表明,镁可能对缺氧损伤具有保护作用。特别是,L-苏糖酸镁 (MgT) 可以比 MgSO4 更好地增加大脑中的镁离子浓度并改善认知功能。我们评估了 MgT 和 MgSO4 处理的人 SH-SY5Y 神经元在缺氧条件下的细胞活力、MgT 处理的斑马鱼缺氧后使用 T 迷宫测试的体内行为、脑线粒体脱氢酶的活性由 2,3,5-氯化三苯基四唑鎓 (TTC) 染色,通过蛋白质印迹分析兴奋性氨基酸转运蛋白 (EAAT) 4 谷氨酸转运蛋白的蛋白质表达。在用缺氧处理的组中,当用 1 或 10 mM MgT 预处理时,细胞活力显着增加(分别为 p = 0.009 和 0.026)。尽管缺氧,但 MgT 处理的斑马鱼表现出对红色隔间的偏好(距离 p = 0.025,进入频率 p = 0.007),表明记忆力得以保留。TTC 染色显示缺氧后 MgT 处理的斑马鱼脑中脑梗塞减少和吸光度保持不变(与缺氧组相比,p = 0.010)。此外,蛋白质印迹显示 MgT 处理组中 EAAT4 蛋白的上调。MgT 预处理可减轻斑马鱼因缺氧引起的细胞死亡和脑梗塞,并保护其认知功能。此外,
更新日期:2020-06-26
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