Hormone deprivation alters mitochondrial function and lipid profile in the hippocampus

ZARATE, SANDRA; ASTIZ, MARIANA; MAGNANI, NATALIA; IMSEN, MERCEDES; MERINO, FLORENCIA; ALVAREZ, SILVIA; REINÉS, ANALÍA; SEILICOVICH, ADRIANA

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2017 vol. 233 p. 1 - 14

0022-0795

Mitochondrial dysfunction is a common hallmark in aging. In the female, reproductivesenescence is characterized by loss of ovarian hormones, many of whose neuroprotectiveeffects converge upon mitochondria. The functional integrity of mitochondria isdependent on membrane fatty acid and phospholipid composition, which are alsoaffected during aging. The effect of long-term ovarian hormone deprivation uponmitochondrial function and its putative association with changes in mitochondrialmembrane lipid profile in the hippocampus, an area primarily affected during agingand highly responsive to ovarian hormones, is unknown. To this aim, Wistar adultfemale rats were ovariectomized or sham-operated. Twelve weeks later, differentparameters of mitochondrial function (O2 uptake, ATP production, membrane potentialand respiratory complex activities) as well as membrane phospholipid content andcomposition were evaluated in hippocampal mitochondria. Chronic ovariectomyreduced mitochondrial O2 uptake and ATP production rates and induced membranedepolarization during active respiration without altering the activity of respiratorycomplexes. Mitochondrial membrane lipid profile showed no changes in cholesterollevels but higher levels of unsaturated fatty acids and a higher peroxidizability indexin mitochondria from ovariectomized rats. Interestingly, ovariectomy also reducedcardiolipin content and altered cardiolipin fatty acid profile leading to a lowerperoxidizability index. In conclusion, chronic ovarian hormone deprivation inducesmitochondrial dysfunction and changes in the mitochondrial membrane lipid profilecomparable to an aging phenotype. Our study provides insights into ovarian hormoneloss-induced early lipidomic changes with bioenergetic deficits in the hippocampus thatmay contribute to the increased risk of