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Decline in Mitochondrial Respiration in Post-Ovariectomy Mice is Ameliorated by Beta Estradiol Treatment: Insights on Alzheimer's Disease
The female sex hormone estrogen has potent neuroprotective properties. Some of these effects may be due to direct modulation of mitochondrial functions. I hypothesized that β-estradiol, a specific hormone of the estrogen family, will improve mitochondrial bioenergetics in ovariectomized mice. Mice (C57BL/6J, female, 4-10 months-old) were ovariectomized via bilateral incision and control animals underwent sham surgery. Ovariectomized mice were divided into two groups. One group received a subcutaneous injection of 17-β-estradiol (E2) dissolved in com oil (30 ng/g) 24 h prior to synaptosome isolation (estradiol group). The second group received com oil alone (OVX). Synaptosomes were isolated from the forebrain by Percoll gradient centrifugation. Oxygen consumption of permeabilized synaptosomes was measured using Clark-type polarographic electrodes at 37°C. Respiration rates under conditions of oxidative phosphorylation (OXPHOS, state 3) were determined in presence of 5 mM pyruvate, 2 mM malate, 10 mM glutamate, 10 mM succinate, and 2 mM ADP. Our results revealed that OXPHOS state 4 rates dropped in OVX mice compared to those receiving the sham surgery. Respiration rates after estrogen treatment increased compared to OVX and were indistinguishable from those in the sham treatment. However, no differences in OXPHOS rates were observed among groups in absence of succinate. My data indicate that E2 directly increases mitochondrial activity. Additional studies should attempt to determine whether succinate dehydrogenase levels are altered by E2 administration.
Fernandez, William L., "Decline in Mitochondrial Respiration in Post-Ovariectomy Mice is Ameliorated by Beta Estradiol Treatment: Insights on Alzheimer's Disease" (2013). Undergraduate Honors Theses. 73.