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首页> 外文期刊>The European Journal of Neuroscience >Energy failure in astrocytes increases the vulnerability of neurons to spreading depression.
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Energy failure in astrocytes increases the vulnerability of neurons to spreading depression.

机译：星形胶质细胞的能量衰竭增加了神经元对抑郁症蔓延的脆弱性。

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Abstract A neuroprotective role of astrocytes has been hypothesized, but the mechanism is debated and in vivo evidence is limited. To test this hypothesis, a sublethal stressor (spreading depression) and fluorocitrate (FC), a selective inhibitor of the astrocytic Krebs cycle, were used in urethane-anaesthetized adult rats. Neuronal damage was assessed 24 h after treatment with silver stain and immunoreactivity for a 72-kDa heat-shock protein. ATP levels and mitochondrial aconitase activity, a marker indicating exposure to reactive oxygen species, were measured after 4 and 24 h. Spreading depression alone did not affect ATP levels, mitochondrial aconitase activity, or induce neuronal injury in the cortex. Local or intraventricular injection of FC significantly decreased ATP levels and mitochondrial aconitase activity, but did not produce neuronal damage. In animals receiving injections of FC and then spreading depression, there was evidence of significant neuronal stress and damage. Isocitrate, which bypasses the metabolic inhibition produced by FC, prevented all of the changes seen after the combination of FC and spreading depression. One-hour pretreatment with dimethyl sulfoxide (a scavenger of hydroxyl radicals), deferoxamine (an iron chelator) or fructose-1,6-bisphosphate also blocked inactivation of mitochondrial aconitase, ATP depletion and the neuronal damage induced by FC and spreading depression. These experiments demonstrate that inhibition of the metabolism of astrocytes, with a decrease in ATP levels, will increase the susceptibility of neurons to the stress induced by spreading depression. The neuroprotective effects of dimethyl sulfoxide, deferoxamine and fructose-1,6-bisphosphate suggest that oxidative stress contributes to the neurotoxicity in this situation.
机译：摘要有人假设星形胶质细胞具有神经保护作用，但其作用机制尚有争议，且体内证据有限。为了验证这一假设，在麻醉了氨基甲酸乙酯的成年大鼠中使用了亚致死应激源（扩散抑郁）和星形胶质细胞克雷布斯循环的选择性抑制剂氟柠檬酸盐（FC）。用银染和72kDa热休克蛋白的免疫反应性处理后24小时评估神经元损伤。在4和24小时后，测量ATP水平和线粒体乌头酸酶活性，这是表明暴露于活性氧的标记。单独传播抑郁并不会影响ATP水平，线粒体乌头酸酶活性或诱导皮质神经元损伤。局部或脑室内注射FC可显着降低ATP水平和线粒体乌头酸酶活性，但不会产生神经元损伤。在接受FC注射然后散布抑郁症的动物中，有明显的神经元压力和损害的证据。异柠檬酸绕过了FC产生的代谢抑制，阻止了FC和散布性抑郁症相结合后出现的所有变化。用二甲亚砜（羟自由基清除剂），去铁胺（铁螯合剂）或果糖1，，6-二磷酸进行一小时的预处理还可以阻止线粒体乌头酸酶的失活，ATP耗竭以及FC引起的神经元损伤和扩散性抑郁。这些实验表明，星形胶质细胞代谢的抑制，随着ATP水平的降低，将增加神经元对由分散性抑郁引起的应激的敏感性。二甲基亚砜，去铁胺和1,6-双磷酸果糖的神经保护作用表明，在这种情况下氧化应激会导致神经毒性。

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