The establishment of an objective and effective approach is imperative for depression diagnosis and anti-depressant efficacy evaluation, which might eliminate the drawbacks of current clinical diagnoses that rest on subjective scales. Oxidative stress may lead to depression with an excess of oxidants, but correspondingly, reductants play essential roles in retaining redox homeostasis, one of which is mitochondrial cysteine (Cys). Therefore, real-time and in situ monitoring of mitochondrial Cys fluctuations in the mouse brain is expected to achieve effective diagnosis and pharmacodynamic evaluation of depression. Herein, we developed a near-infrared fluorescence imaging probe (CSS) for the detection of mitochondrial Cys in the mouse brain. CSS is responsive to changes in the level of Cys at 705 nm and has high sensitivity, selectivity, temporal–spatial resolution and deep tissue penetration. Utilizing the probe, we revealed that the concentration of mitochondrial Cys decreased in the brains of mice with depression. Importantly, in the brains of depressed mice with three antidepressants, varying levels of Cys were observed, indicating different antidepressant efficacies. Altogether, this work affords a convincing strategy for the precise diagnosis of depression and pharmacodynamic evaluation of antidepressants.

中文翻译：

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通过近红外荧光成像，基于通量线粒体半胱氨酸在活小鼠体内的抗抑郁药的体内药效学评估。

建立客观有效的方法对于抑郁症的诊断和抗抑郁药的疗效评估是必不可少的，这可能会消除目前基于主观尺度的临床诊断的弊端。氧化应激可能会导致氧化剂过量而导致抑郁，但是相应地，还原剂在保持氧化还原稳态方面起着至关重要的作用，其中之一就是线粒体半胱氨酸（Cys）。因此，实时和原位监测小鼠脑线粒体Cys的波动有望实现抑郁症的有效诊断和药效学评估。本文中，我们开发了一种近红外荧光成像探针（CSS），用于检测小鼠脑中的线粒体Cys。CSS对705 nm处Cys水平的变化有反应，并具有高灵敏度，选择性，时空分辨率和深层组织穿透性。利用该探针，我们发现抑郁症小鼠的大脑中线粒体半胱氨酸的浓度降低了。重要的是，在患有三种抗抑郁药的抑郁小鼠的大脑中，观察到的Cys水平不同，表明抗抑郁药的功效不同。共，