Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital, Seoul, Korea.
Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Ansan, Korea.
BMC Neurosci. 2020 Jun 26;21(1):29. doi: 10.1186/s12868-020-00580-6.
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 MgSO and improve cognitive function.
We evaluated cell viability under hypoxic conditions in the MgT- and MgSO-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.
缺氧会抑制谷氨酸（大脑中的一种主要神经递质，与认知功能密切相关）进入脑细胞，而细胞对皮质缺氧的初始反应取决于谷氨酸。先前的研究表明，镁可能对缺氧损伤具有保护作用。特别是，镁 L-苏糖酸酯（MgT）可能比 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 处理的斑马鱼在缺氧后的 T 迷宫测试中的体内行为、2,3,5-三苯基氯化四氮唑（TTC）染色的脑线粒体脱氢酶活性以及 Western 印迹法测定的兴奋性氨基酸转运蛋白（EAAT）4 谷氨酸转运蛋白的蛋白表达。
在缺氧处理的各组中，当用 1 或 10 mM MgT 预处理时，细胞活力显著增加（p=0.009 和 0.026）。尽管受到缺氧的影响，MgT 处理的斑马鱼仍然偏爱红色隔间（距离的 p=0.025，进入的频率的 p=0.007），表明记忆保存。TTC 染色显示缺氧后 MgT 处理的斑马鱼大脑中的脑梗死减少且吸收保留（与缺氧组相比，p=0.010）。此外，Western blot 显示 MgT 处理组的 EAAT4 蛋白表达上调。
MgT 预处理可减轻缺氧引起的细胞死亡和脑梗死，并保护斑马鱼的认知功能。此外，MgT 似乎调节了谷氨酸转运蛋白 EAAT4 的表达。
