Correlations Among mRNA Expression Levels of ATP7A, Serum Ceruloplasmin Levels, and Neuronal Metabolism in Unmedicated Major Depressive Disorder.
Correlations Among mRNA Expression Levels of ATP7A, Serum Ceruloplasmin Levels, and Neuronal Metabolism in Unmedicated Major Depressive Disorder.
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未经药物治疗的重度抑郁症中 ATP7A mRNA 表达水平、血清铜蓝蛋白水平和神经元代谢之间的相关性
DOI：
10.1093/ijnp/pyaa038
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发表时间：
2020-12-10
期刊：
影响因子：
--
通讯作者：
Jia Y
中科院分区：
文献类型：
--
作者：
Liu X;Zhong S;Yan L;Zhao H;Wang Y;Hu Y;Jia Y
摘要背景先前的研究发现，铜水平升高会导致氧化，这与严重抑郁障碍(MDD)的发生有关。然而，MDD患者脑代谢异常的机制尚不清楚。ATP7A酶的主要功能是跨膜转运铜以保持铜的动态平衡，这与精神障碍和认知障碍的发生密切相关。然而，关于MDD患者中ATP7A表达的相关性还知之甚少。方法研究对象为31例MDD患者和21例健康对照。用质子磁共振波谱分析感兴趣区的N-乙酰天冬氨酸、胆碱(Cho)和肌酸(Cr)的浓度水平，包括前额叶白质(PWM)、前扣带回皮质(ACC)、丘脑、豆状核和小脑。用聚合酶链式反应(SYBR Green法)检测ATP7A的mRNA表达水平。研究ATP7A和/或铜蓝蛋白的mRNA表达水平与感兴趣区神经元生化代谢物比率的相关性。结果MDD患者ATP7A基因表达水平下降与铜蓝蛋白水平升高呈正相关。此外，在MDD患者中，ATP7A基因表达水平的下降与左侧脉宽调制、右侧脉宽调制和右侧ACC的Cho/Cr比值升高呈负相关。在MDD患者中，铜蓝蛋白水平升高与左侧脉宽调制Cho/Cr比值升高呈正相关。结论MDD患者脑组织中ATP7A基因表达水平下降，铜蓝蛋白水平升高，氧化损伤导致脑神经元代谢紊乱，在MDD的病理生理机制中起重要作用。MDD患者左侧PWM、右侧PWM和右侧ACC中ATP7A基因表达水平的下降和铜蓝蛋白水平的升高影响了神经细胞膜的代谢损伤。
Abstract Background Previous studies have found that elevated copper levels induce oxidation, which correlates with the occurrence of major depressive disorder (MDD). However, the mechanism of abnormal cerebral metabolism of MDD patients remains ambiguous. The main function of the enzyme ATPase copper-transporting alpha (ATP7A) is to transport copper across the membrane to retain copper homeostasis, which is closely associated with the onset of mental disorders and cognitive impairment. However, less is known regarding the association of ATP7A expression in MDD patients. Methods A total of 31 MDD patients and 21 healthy controls were recruited in the present study. Proton magnetic resonance spectroscopy was used to assess the concentration levels of N-acetylaspartate, choline (Cho), and creatine (Cr) in brain regions of interest, including prefrontal white matter (PWM), anterior cingulate cortex (ACC), thalamus, lentiform nucleus, and cerebellum. The mRNA expression levels of ATP7A were measured using polymerase chain reaction (SYBR Green method). The correlations between mRNA expression levels of ATP7A and/or ceruloplasmin levels and neuronal biochemical metabolite ratio in the brain regions of interest were evaluated. Results The decline in the mRNA expression levels of ATP7A and the increase in ceruloplasmin levels exhibited a significant correlation in MDD patients. In addition, negative correlations were noted between the decline in mRNA expression levels of ATP7A and the increased Cho/Cr ratios of the left PWM, right PWM, and right ACC in MDD patients. A positive correlation between elevated ceruloplasmin levels and increased Cho/Cr ratio of the left PWM was noted in MDD patients. Conclusions The findings suggested that the decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels induced oxidation that led to the disturbance of neuronal metabolism in the brain, which played important roles in the pathophysiology of MDD. The decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels affected neuronal membrane metabolic impairment in the left PWM, right PWM, and right ACC of MDD patients.
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DOI：
10.1016/j.plefa.2009.12.002
发表时间：
2010-02
期刊：
Prostaglandins, leukotrienes, and essential fatty acids
影响因子：
--
作者：
Conklin SM;Runyan CA;Leonard S;Reddy RD;Muldoon MF;Yao JK
通讯作者：
Yao JK
帕金森病脑脊液液中的Ceruloplasmin功能变化。
影响因子：
15.1
作者：
Barbariga M;Curnis F;Andolfo A;Zanardi A;Lazzaro M;Conti A;Magnani G;Volontè MA;Ferrari L;Comi G;Corti A;Alessio M
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影响因子：
6.6
作者：
Lai, Shunkai;Zhong, Shuming;Jia, Yanbin
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自愿跑轮可以改善慢性不可预测的轻度应激小鼠的抑郁样行为和脑血氧水平依赖性信号。
影响因子：
2.7
作者：
Huang, Peng;Dong, Zhaoyang;Lv, Zhiping
通讯作者：
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影响因子：
7
作者：
Gujral S;Aizenstein H;Reynolds CF 3rd;Butters MA;Erickson KI
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Erickson KI