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Roles of astroglial energy metabolism in ischemic neuronal cell damage: an implication for the treatment of cerebral ischemia

星形胶质细胞能量代谢在缺血性神经细胞损伤中的作用：对脑缺血治疗的启示

基本信息

批准号：
11470149
负责人：
TAKEDA Hidetaka
金额：
$ 8.77万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470149/
关键词：
ASTROCYTE NEURON GLUCOSE GLYCOGEN PYRUVATE LACTATE MTT Alamar Blue 虚血 TCA回路 Naイオンオリゴデンドロサイト LDH SBFI ミトコンドリア

项目摘要

1) Persistent activation of voltage-sensitive sodium channels results in Na^+ influx into rat cultured neurons and induces neuronal cell damage. Sodium ionophore also induces Na^+ -induced neuronal damage.2) Na^+ influx causes astroglial cell damage via its mitochondrial dysfunction. The mechanism by which Na^+ influx induces cell damage in astroglia is different from that in neurons.3) 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction is interpreted to be indicative of cellular metabolic activity. MTT specific activity of astroglia was much higher than that of neurons. In astroglia, MTT reduction reflects mainly cytosolic redox activity and is dependent on glyceraldehyde 3-phosphate dehydrogenase. In neurons, pyruvate dehydrogenase supports MTT reduction more effectively than glucose or lactate, even though both of these substrates can produce NADH and pyruvate.4) Glucose is the sole energy source of the brain. In brain, only astrocytes can store glucose as intracellular glycogen and utilize it when glucose supply is limited. We examined the effect of acute or chronic exposure to glucose depleted condition on intracellular glycogen content and the reduction of Alamar Blue, an indicator of cellular energy metabolism, in rat cultured astroglia. Obtained results suggest that astroglial energy production becomes more dependent on the TCA cycle when extracellular glucose and intracellular glycogen are not available.

1)电压敏感性钠通道的持续激活导致Na^+内流进入大鼠培养的神经元，并诱导神经元细胞损伤。钠离子载体也可诱导Na^+诱导的神经元损伤。2）Na^+内流通过线粒体功能障碍引起星形胶质细胞损伤。Na^+内流诱导星形胶质细胞损伤的机制与神经元不同。3）3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑（MTT）还原被解释为细胞代谢活性的指示。星形胶质细胞的MTT比活性明显高于神经元。在星形胶质细胞中，MTT还原主要反映胞质氧化还原活性，并依赖于甘油醛3-磷酸脱氢酶。在神经元中，丙酮酸脱氢酶比葡萄糖或乳酸更有效地支持MTT还原，即使这两种底物都可以产生NADH和琥珀酸。4）葡萄糖是大脑的唯一能量来源。在脑中，只有星形胶质细胞可以将葡萄糖储存为细胞内糖原，并在葡萄糖供应受限时利用它。我们研究了急性或慢性暴露于葡萄糖耗尽条件下对大鼠培养的星形胶质细胞中细胞内糖原含量和细胞能量代谢指标Alcohol Blue减少的影响。所获得的结果表明，星形胶质细胞的能量生产变得更加依赖于TCA循环时，细胞外葡萄糖和细胞内糖原不可用。