BACKGROUND Previous studies have found that the 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 in order to retain copper homeostasis, which is closely associated with the onset of mental disorders and cognitive impairment. Nevertheless, less is known regarding the association of ATP7A expression in MDD patients. METHODS A total of 31 MDD patients and 21 healthy controls (HC) were recruited in the present study. Proton magnetic resonance spectroscopy (1H-MRS) was used to assess the concentration levels of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) in brain regions of interest, including prefrontal whiter matter (PWM), anterior cingulate cortex (ACC), thalamus, lentiform nucleus (LN) and cerebellum. The mRNA expression levels of ATP7A were measured using polymerase chain reaction (SYBR Green method). The correlations between the 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 leading 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.

中文翻译：

---

未用药的重度抑郁症患者 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。

背景 先前的研究发现，升高的铜水平会引起氧化，这与重度抑郁症 (MDD) 的发生有关。然而，MDD患者脑代谢异常的机制尚不明确。ATPase 铜转运α (ATP7A) 酶的主要功能是跨膜转运铜以保持铜稳态，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 表达的关联知之甚少。方法 本研究共招募了 31 名 MDD 患者和 21 名健康对照 (HC)。质子磁共振波谱 (1H-MRS) 用于评估 N-乙酰天冬氨酸 (NAA) 的浓度水平，感兴趣的大脑区域中的胆碱 (Cho) 和肌酸 (Cr)，包括前额叶白质 (PWM)、前扣带皮层 (ACC)、丘脑、豆状核 (LN) 和小脑。使用聚合酶链反应（SYBR Green 方法）测量 ATP7A 的 mRNA 表达水平。评估了感兴趣的大脑区域中 ATP7A 和/或铜蓝蛋白水平的 mRNA 表达水平与神经元生化代谢物比率之间的相关性。结果 ATP7A mRNA 表达水平的下降和铜蓝蛋白水平的增加在MDD 患者中表现出显着的相关性。此外，在 MDD 患者中，ATP7A mRNA 表达水平的下降与左侧 PWM、右侧 PWM 和右侧 ACC 的 Cho/Cr 比率增加之间存在负相关。在 MDD 患者中注意到血浆铜蓝蛋白水平升高与左侧脉宽调制的 Cho/Cr 比值升高之间呈正相关。结论 研究结果表明，ATP7A mRNA 表达水平的下降和血浆铜蓝蛋白水平的升高诱导氧化，导致大脑神经元代谢紊乱，这在 MDD 的病理生理学中起重要作用。ATP7A mRNA 表达水平的下降和铜蓝蛋白水平的升高影响了 MDD 患者左侧 PWM、右侧 PWM 和右侧 ACC 的神经元膜代谢障碍。结论 研究结果表明，ATP7A mRNA 表达水平的下降和血浆铜蓝蛋白水平的升高诱导氧化，导致大脑神经元代谢紊乱，这在 MDD 的病理生理学中起重要作用。ATP7A mRNA 表达水平的下降和铜蓝蛋白水平的升高影响了 MDD 患者左侧 PWM、右侧 PWM 和右侧 ACC 的神经元膜代谢障碍。结论 研究结果表明，ATP7A mRNA 表达水平的下降和血浆铜蓝蛋白水平的升高诱导氧化，导致大脑神经元代谢紊乱，这在 MDD 的病理生理学中起重要作用。ATP7A mRNA 表达水平的下降和铜蓝蛋白水平的升高影响了 MDD 患者左侧 PWM、右侧 PWM 和右侧 ACC 的神经元膜代谢障碍。