Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.
Neurosci Lett. 2011 Jan 13;488(1):76-80. doi: 10.1016/j.neulet.2010.11.006. Epub 2010 Nov 9.
Increasing evidence implicates mitochondrial failure as a crucial factor in the pathogenesis of mental disorders, such as depression. The aim of the present study was to investigate the effects of exposure to chronic mild stress (CMS), a paradigm developed in the late 1980s as an animal model of depression, on the mitochondrial function and mitochondrial ultrastructure in the mouse brain. The results showed that the CMS regime induced depressive-like symptoms in mice characterized by reduced sucrose preference and body weight. Moreover, CMS exposure was associated with a significant increase in immobility time in the tail suspension test. Exposure to the CMS paradigm inhibited mitochondrial respiration rates and dissipated mitochondrial membrane potential in hippocampus, cortex and hypothalamus of mice. In addition, we found a damaged mitochondrial ultrastructure in brains of mice exposed to CMS. These findings provide evidence for brain mitochondrial dysfunction and ultrastructural damage in a mouse model of depression. Moreover, these findings suggest that mitochondrial malfunction-induced oxidative injury could play a role in stress-related disorders such as depression.
越来越多的证据表明，线粒体功能衰竭是精神障碍（如抑郁症）发病机制中的一个关键因素。本研究旨在探讨慢性轻度应激（CMS）暴露对小鼠大脑中线粒体功能和超微结构的影响，CMS 是上世纪 80 年代末开发的一种抑郁症动物模型。结果表明，CMS 处理方案诱导了具有减少蔗糖偏好和体重的抑郁样症状的小鼠。此外，CMS 暴露与尾部悬垂试验中不动时间的显著增加有关。CMS 处理方案抑制了小鼠海马体、皮质和下丘脑中线粒体呼吸率，并耗散了线粒体膜电位。此外，我们发现 CMS 处理的小鼠大脑中线粒体超微结构受损。这些发现为抑郁模型中小鼠的脑线粒体功能障碍和超微结构损伤提供了证据。此外，这些发现表明，线粒体功能障碍引起的氧化损伤可能在应激相关疾病（如抑郁症）中发挥作用。
