Estradiol Replacement Modulates Synaptic Transmission-Related Proteins in the Hippocampus of Ovariectomized Rats: An...

The loss of ovarian hormones in postmenopause influences cognition, emotion and energy homeostasis, processes integrated by the hippocampus. The mechanisms by which estradiol influences this area have not been fully understood. The present study aimed at investigating the effects of estradiol on the rat hippocampus proteome of ovariectomy-induced menopause either followed by estradiol replacement or not. Eighteen 3-month-old female Wistar rats were either ovariectomized or sham operated and fed with standard chow for 3 months. A subgroup of ovariectomized rats received estradiol replacement. The hippocampi were processed using data independent acquisition MS-based proteomics and differentially expressed proteins were submitted to bioinformatics analysis for a pathway-based functional understanding of the estradiol effects. Proteomic analysis revealed that 49 hippocampal proteins were modulated by ovariectomy and estradiol replacement. Functional analysis of the differentially expressed proteins revealed the enrichment of terms related to energy metabolism (comprising glycolysis/gluconeogenesis, pyruvate metabolism, oxidative phosphorylation, and response to oxidative stress) and neuron projection (comprising cytoskeleton organization, regulation of vesicle-mediated transport, and modulation of chemical synaptic transmission). The present dataset indicates that, at the hippocampus, estradiol affects mitochondrial dynamics, lipid metabolism and intracellular trafficking machinery and influences dendritic and synaptic transmission and brain plasticity. Some alterations observed in proteins have not yet been described in the hippocampus in the context of menopause and estradiol replacement. These data provide new insights into the mechanisms involved with menopause effects and may help future studies related to drug development for the prevention and treatment of postmenopause associated symptoms.