山东师范大学唐波课题组发现，小鼠脑中过氧化物酶体超氧阴离子自由基介导的色氨酸羟化酶氧化损伤可能与抑郁症有关。 2020年11月25日，国际知名学术期刊《美国化学会志》发表了这一成果。

在该研究中，课题组开发了一种双光子荧光探针TCP，用于实时可视化过氧化物酶体中首次产生的活性氧（ROS）超氧阴离子自由基（O₂^·-）。利用双光子荧光成像，研究小组发现小鼠脑中过氧化物酶体的O₂^·-在氧化应激过程中升高，导致过氧化氢酶（CAT）失活。随后，细胞内过氧化氢水平升高，进一步导致了色氨酸羟化酶2（TPH2）的氧化。TPH2含量的降低进而导致小鼠脑内5-羟色胺（5-HT）系统功能障碍，最终导致抑郁样行为。

这项工作提供了抑郁症中过氧化物酶体O₂^·-介导的信号通路的证据，将有助于确定潜在的抑郁症治疗靶标。

据了解，抑郁与大脑中的氧化应激密切相关。过氧化物酶体通过维持活性氧稳态在调节细胞内氧化还原平衡中发挥重要作用。现有证据提示，过氧化物酶体活性氧可能与抑郁症有关。尽管如此，由于现有检测方法的局限性，抑郁症中过氧化物酶体活性氧的潜在调节机理仍不完善。

附：英文原文

Title: Oxidative Damage of Tryptophan Hydroxylase-2 Mediated by Peroxisomal Superoxide Anion Radical in Brains of Mouse with Depression

Author: Qi Ding, Ying Tian, Xin Wang, Ping Li, Di Su, Chuanchen Wu, Wen Zhang, Bo Tang

Issue&Volume: November 25, 2020

Abstract: Depression is intimately linked with oxidative stress in the brains. Peroxisome plays vital roles in the regulation of intracellular redox balance by keeping reactive oxygen species (ROS) homeostasis. Available evidence indicates a possible relationship between peroxisomal ROS and depression. Even so, the underlying modulation mechanisms of peroxisomal ROS in depression are still rudimentary due to the limitations of the existing detecting methods. Hence, we developed a two-photon fluorescent probe TCP for the real-time visualization of the first produced ROS superoxide anion radical (O2·–) in peroxisome. Using the two-photon fluorescence imaging, we found that peroxisomal O2·– rose during oxidative stress in the mouse brains, resulting in the inactivation of catalase (CAT). Subsequently, the intracellular H2O2 level elevated, which further oxidized tryptophan hydroxylase-2 (TPH2). Then the decrease contents of TPH2 caused the dysfunction of 5-hydroxytryptamine (5-HT) system in the mouse brains, eventually leading to depression-like behaviors. Our work provides evidence of a peroxisomal O2·– mediated signaling pathway in depression, which will conduce to pinpoint potential targets for the treatment of depression.

DOI: 10.1021/jacs.0c09576

Source: https://pubs.acs.org/doi/10.1021/jacs.0c09576