Evidence for impaired glucose metabolism in the striatum, obtained postmortem, from some subjects with schizophrenia.
Evidence for impaired glucose metabolism in the striatum, obtained postmortem, from some subjects with schizophrenia.
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DOI：
10.1038/tp.2016.226
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发表时间：
2016-11-15
影响因子：
6.8
通讯作者：
Udawela M
中科院分区：
文献类型：
--
作者：
Dean B;Thomas N;Scarr E;Udawela M
使用死后获得的中枢神经系统组织进行的研究表明，能量和代谢途径参与精神分裂症的病理生理学;神经影像学研究表明，葡萄糖代谢尤其受到纹状体的影响。为了获得有关纹状体葡萄糖代谢途径状态的信息，我们测量了精神分裂症受试者和年龄/性别匹配对照组死后组织中葡萄糖、丙酮酸、乙酰辅酶A和乳酸以及丙酮酸脱氢酶β亚基（一种限速酶）的水平。精神分裂症受试者由两个亚组组成，这两个亚组可以被划分，因为他们要么有（毒蕈碱受体缺陷型精神分裂症（MRDS）），要么没有（非MRDS），皮质毒蕈碱受体明显缺陷。与对照组相比，精神分裂症受试者纹状体中丙酮酸脱氢酶β亚基的水平较低（Δ平均值=-20%），丙酮酸（Δ平均值=+47%）和乳酸（Δ平均值=+15%）的水平显著较高。值得注意的是，在非MRDS受试者中，纹状体丙酮酸脱氢酶β亚基水平较低（Δ平均值=−29%），而丙酮酸（Δ平均值=−66%），乙酰辅酶A（Δ平均值=−28%）和葡萄糖（Δ平均值=-27%）水平较高，而乳酸（Δ平均值=+17%）水平较高。最后，使用丙酮酸脱氢酶β亚基和葡萄糖的水平，或更好的是，丙酮酸脱氢酶β亚基和葡萄糖与丙酮酸、乳酸或乙酰辅酶A的组合进行判别分析，可以以高水平的特异性（高达93%）和选择性（高达91%）将非MRDS受试者与对照者区分开来。我们的数据显示，能够研究精神分裂症综合征中定义的亚组的益处，因为这种方法揭示了葡萄糖代谢的变化可能是非MRDS病理生理学的重要贡献者。
Studies using central nervous system tissue obtained postmortem suggest pathways involved in energy and metabolism contribute to the pathophysiology of schizophrenia; neuroimaging studies suggesting glucose metabolism is particularly affected in the striatum. To gain information on the status of pathways involved in glucose metabolism in the striatum, we measured levels of glucose, pyruvate, acetyl-CoA and lactate as well as the β subunit of pyruvate dehydrogenase, a rate limiting enzyme, in the postmortem tissue from subjects with schizophrenia and age/sex-matched controls. The subjects with schizophrenia were made up of two subgroups, which could be divided because they either had (muscarinic receptor deficit schizophrenia (MRDS)), or did not have (non-MRDS), a marked deficit in cortical muscarinic receptors. Compared to controls, levels of β subunit of pyruvate dehydrogenase were lower (Δ mean=−20%) and levels of pyruvate (Δ mean=+47%) and lactate (Δ mean=+15%) were significantly higher in the striatum from subjects with schizophrenia. Notably, in subjects with non-MRDS, striatal levels of β subunit of pyruvate dehydrogenase were lower (Δ mean=−29%), whereas levels of pyruvate (Δ mean=−66%), acetyl-CoA (Δ mean=−28%) and glucose (Δ mean=-27%) were higher, whereas levels of lactate (Δ mean=+17%) were higher in MRDS. Finally, discriminate analyses using levels the β subunit of pyruvate dehydrogenase and glucose, or better still, β subunit of pyruvate dehydrogenase and glucose in combination with pyruvate, lactate or acetyl-CoA could separate subjects with non-MRDS from controls with high levels of specificity (up to 93%) and selectivity (up to 91%). Our data show the benefit of being able to study defined subgroups within the syndrome of schizophrenia as such an approach has revealed that changes in glucose metabolism may be a significant contributor to the pathophysiology of non-MRDS.