In vivo evidence for cerebral depletion in high-energy phosphates in progressive supranuclear palsy
In vivo evidence for cerebral depletion in high-energy phosphates in progressive supranuclear palsy
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DOI：
10.1038/jcbfm.2009.2
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发表时间：
2009-04-01
影响因子：
6.3
通讯作者：
Hoeglinger, Guenter U.
中科院分区：
文献类型：
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作者：
Stamelou, Maria;Pilatus, Ulrich;Hoeglinger, Guenter U.
来自实验室的间接证据表明，进行性核上性麻痹(PSP)患者的线粒体能量代谢受损，但目前还没有对患者进行全面的体内直接能量代谢研究。我们使用联合磷和质子磁共振波谱测定了临床可能的患者(N=21；PSP分期II至III)和健康对照组(N=9)基底节和额叶和枕叶中的三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、磷酸化肌酸、非磷酸化肌酸、无机磷和乳酸。在PSP患者受肌酸严重影响的基底节，高能磷酸盐(=ATP+磷酸化肌酸)和无机磷的浓度降低，但低能磷酸盐(=ADP+非磷酸化肌酸)的浓度没有下降。这一下降可能并不反映神经元死亡，因为在接受检查的早期患者中，神经元标记物N-乙酰天冬氨酸尚未显著降低。在PSP中，额叶也容易出现神经变性，表现出类似的改变，而枕叶，通常不受影响，表现出较不明显的改变。35%的患者乳酸水平升高，乳酸是厌氧糖酵解的产物。观察到的PSP中脑能量代谢产物水平的变化与氧化磷酸化功能相关的损害是一致的。
Indirect evidence from laboratory studies suggests that mitochondrial energy metabolism is impaired in progressive supranuclear palsy (PSP), but brain energy metabolism has not yet been studied directly in vivo in a comprehensive manner in patients. We have used combined phosphorus and proton magnetic resonance spectroscopy to measure adenosine-triphosphate (ATP), adenosine-diphosphate (ADP), phosphorylated creatine, unphosphorylated creatine, inorganic phosphate and lactate in the basal ganglia and the frontal and occipital lobes of clinically probable patients (N = 21; PSP stages II to III) and healthy controls (N = 9). In the basal ganglia, which are severely affected creatine in PSP patients, the concentrations of high-energy phosphates (= ATP + phosphorylated creatine) and inorganic phosphate, but not low-energy phosphates (= ADP + unphosphorylated creatine), were decreased. The decrease probably does not reflect neuronal death, as the neuronal marker N-acetylaspartate was not yet significantly reduced in the early-stage patients examined. The frontal lobe, also prone to neurodegeneration in PSP, showed similar alterations, whereas the occipital lobe, typically unaffected, showed less pronounced alterations. The levels of lactate, a product of anaerobic glycolysis, were elevated in 35% of the patients. The observed changes in the levels of cerebral energy metabolites in PSP are consistent with a functionally relevant impairment of oxidative phosphorylation.