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Brain Mitochondrial Dysfunction in Ovariectomized Mice Injected with d-Galactose

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Abstract

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 (F1F0-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.

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Acknowledgments

This work was supported by the grants from National Key Basic Research Program of China (2009CB521906), Natural Science Foundation of Jiangsu Province (BK2006576) and Jiangsu Qing Lan Project.

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Correspondence to Ming Xiao.

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11064_2009_68_MOESM1_ESM.tif

Morris water-maze testing. (A) Mean latency in the hidden platform test. (B) Comparison of time spent in the target quadrant with other quadrants on day 5. Data are expressed as means ± SEM from 16 mice per group. Comparisons between the two groups were made by using Student’s t-test. Multiple comparisons were performed using repeated measures analysis of variance followed by Bonferroni correction. *P < 0.05, **P < 0.01, OVX plus d-gal-injected group versus sham-operated plus saline-injected group (TIFF 1715 kb)

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Su, Y., Sun, H., Fang, J. et al. Brain Mitochondrial Dysfunction in Ovariectomized Mice Injected with d-Galactose. Neurochem Res 35, 399–404 (2010). https://doi.org/10.1007/s11064-009-0068-8

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