South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
J Psychiatr Res. 2019 Jul;114:55-66. doi: 10.1016/j.jpsychires.2019.04.008. Epub 2019 Apr 23.
Chronic stress-induced anxiety disorder is a highly-prevalent, modern social disease in which oxidative stress plays an important role. It is necessary to determine the underlying mechanisms governing this disorder to establish an effective treatment target for anxiety disorders. In this study, we examined the behavioral changes in mice subjected to chronic mild stress (CMS). We found that CMS exposure leads to anxiety-like phenotypes and increased levels of oxidative stress in the ventral hippocampus of mice. Furthermore, CMS increased the excitatory synaptic transmission of pyramidal cells in the ventral CA1 (vCA1). Administration of 4-hydroxy-3-methoxy-acetophenone (apocynin), an inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, clearly ameliorated the changes induced by CMS exposure. In addition, our results of behavioral tests and analyses of reactive oxygen species (ROS) using NOX2-deficient mice indicate that CMS-induced enhanced oxidative stress level is primarily caused by the increased expression of NOX2. NOX2-derived oxidative stress can serve as a target for anxiety therapy led by chronic stress.
慢性应激诱导的焦虑症是一种高发的现代社会疾病，其中氧化应激起着重要作用。有必要确定这种疾病的潜在机制，以便为焦虑症建立有效的治疗靶点。在这项研究中，我们观察了慢性轻度应激（CMS）小鼠的行为变化。我们发现 CMS 暴露导致小鼠腹侧海马区出现类似焦虑的表型和氧化应激水平升高。此外，CMS 增加了腹侧 CA1（vCA1）锥体神经元的兴奋性突触传递。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂 4-羟基-3-甲氧基苯乙酮（apocynin）的给药明显改善了 CMS 暴露引起的变化。此外，我们使用 NOX2 缺陷型小鼠进行的行为测试和活性氧（ROS）分析结果表明，CMS 诱导的氧化应激水平升高主要是由于 NOX2 表达增加所致。NOX2 衍生的氧化应激可以作为慢性应激引起的焦虑症治疗的靶点。
