Abnormalities in the tricarboxylic acid (TCA) cycle in the brains of schizophrenia patients.
Abnormalities in the tricarboxylic acid (TCA) cycle in the brains of schizophrenia patients.
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DOI：
10.1016/j.euroneuro.2010.10.007
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发表时间：
2011-03
影响因子：
5.6
通讯作者：
Blass, J. P.
中科院分区：
文献类型：
--
作者：
Bubber, P.;Hartounian, V.;Gibson, G. E.;Blass, J. P.
大脑新陈代谢的图像和电子传输链组件活动的测量支持了早期的研究，即在相当大比例的精神分裂症患者中，大脑葡萄糖氧化天生异常。因此，我们测定了13例精神分裂症患者和13例非精神病者背外侧前额叶皮质中丙酮酸脱氢酶复合体(PDHC)、柠檬酸合成酶(CS)、乌头酸酶、异柠檬酸脱氢酶(ICDH)、α-酮戊二酸脱氢酶复合体(KGDHC)、琥珀酸硫激酶(STH)、琥珀酸脱氢酶(SDH)、延胡索酶和苹果酸脱氢酶(MDH)的活性。TCA循环前半段的乌头酸酶(18.4%，p<；0.05)、康桂酸脱氢酶(26%)和短链淀粉酶(28.2%，p；0.05)活性较低，而后半段的琥珀酸脱氢酶(18.3%，p<；0.05)和甲基二氢化氢酶(34%，p<；0.005)活性高于对照。PDHC、CS、ICDH和延胡索酸酶活性无明显变化。TCA循环酶活性与认知功能、年龄、胆碱乙酰转移酶活性均无显著相关性，但乌头酸酶活性随年龄增长略有下降(r=0.55，p=003)。脱氢酶活性在三氯乙酸循环的后半段增加，可能反映了对上半段酶活性降低的代偿反应。TCA循环各部分的这种改变足以改变大脑新陈代谢的速度。这些结果与精神分裂症低代谢的影像研究是一致的。他们提出，线粒体酶的缺陷可能与精神分裂症的精神疾病有关。
Images of brain metabolism and measurements of activities of components of the electron transport chain support earlier studies that suggest that brain glucose oxidation is inherently abnormal in a significant proportion of persons with schizophrenia. Therefore, we measured activities of enzymes of the tricarboxylic (TCA) cycle in dorsolateral-prefrontal-cortex from schizophrenia patients (N=13) and non-psychiatric disease controls (N=13): the pyruvate dehydrogenase complex (PDHC), citrate synthase (CS), aconitase, isocitrate dehydrogenase (ICDH), the alpha-ketoglutarate dehydrogenase complex (KGDHC), succinate thiokinase (STH), succinate dehydrogenase (SDH), fumarase and malate dehydrogenase (MDH). Activities of aconitase (18.4%, p<0.05), KGDHC (26%) and STH (28.2%, p<0.05), enzymes in the first half of the TCA cycle, were lower, but SDH (18.3%, p<0.05) and MDH (34%, p<0.005), enzymes in the second half, were higher than controls. PDHC, CS, ICDH and fumarase activities were unchanged. There were no significant correlations between enzymes of TCA cycle and cognitive function, age or choline acetyl transferase activity, except for aconitase activity which decreased slightly with age (r=0.55, p=003). The increased activities of dehydrogenases in the second half of the TCA cycle may reflect a compensatory response to reduced activities of enzymes in the first half. Such alterations in the components of TCA cycle are adequate to alter the rate of brain metabolism. These results are consistent with the imaging studies of hypometabolism in schizophrenia. They suggest that deficiencies in mitochondrial enzymes can be associated with mental disease that takes the form of schizophrenia.
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影响因子：
4.5
作者：
Kirkpatrick, Brian;Fernandez-Egea, Emilio;Garcia-Rizo, Clemente;Bernardo, Miguel
通讯作者：
Bernardo, Miguel
影响因子：
10.6
作者：
Friedman, JI;Harvey, PD;Davis, KL
通讯作者：
Davis, KL
影响因子：
17.7
作者：
Gluck, MR;Thomas, RG;Haroutunian, V
通讯作者：
Haroutunian, V
DOI：
10.1073/pnas.081071198
发表时间：
2001-04-10
影响因子：
11.1
作者：
Hakak, Y;Walker, JR;Fienberg, AA
通讯作者：
Fienberg, AA
影响因子：
11
作者：
Clark, D;Dedova, I;Matsumoto, I
通讯作者：
Matsumoto, I