Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain.
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.
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.
Yu
Y
Gong
Yi
Y
Chai
Jian-Hua
JH
Ding
Xiu-Lan
XL
Sun
Gang
G
Hu
D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D019417:Hindlimb Suspension; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012119:Respiration; D013315:Stress, Psychological / Q000473:pathology* / Q000503:physiopathology
D017382:Reactive Oxygen Species