Brain mitochondrial dysfunction in ovariectomized mice injected with D-galactose.
Our previous studies reveal that long-term exposure of ovariectomized rodents to D: -galactose results in pathophysiologic alterations associated with Alzheimer's disease. The current study was to address whether mitochondrial dysfunction was involved in the pathogenesis of this model. Ovariectomized mice were administered intraperitoneally with D: -galctose (100 mg/kg body weight) once a day for 8 weeks. Brain tissues from model mice showed decreases in reduced glutathione level, total antioxidative capabilities, total superoxide dismutase activity and glutathione peroxidase activity but an increase in malondialdehyde level, compared with those from sham-operated plus saline-injected mice. Activities of brain mitochondrial respiratory chain (complex I, II, III and IV) were reduced in model group. In contrast, ATP synthase (F(1)F(0)-ATPase) activity was not significantly different between the two groups. Moreover, electron microscopy identified ultrastructural impairments of hippocampal mitochondria in model mice. These results demonstrated that brain mitochondrial degeneration caused by oxidative stress participated in the etiology of ovarian hormone deprivation and D-galactose-induced neurodegeneration.
Jiangsu Key Laboratory of Neurodegeneration, Department of Anatomy, Histology and Pharmacology, Nanjing Medical University, 210029, Nanjing, Jiangsu, People's Republic of China.
Yang
Y
Su
Hao
H
Sun
Jie
J
Fang
Gang
G
Hu
Ming
M
Xiao
D025181:ATP Synthetase Complexes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D004579:Electron Transport / Q000187:drug effects; D005260:Female; D005690:Galactose / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects
D000975:Antioxidants; D025181:ATP Synthetase Complexes; D005690:Galactose