Jul 2, 2004

Hippocampal synapses depend on hippocampal estrogen synthesis

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Oliver KretzGabriele M Rune

Abstract

Estrogens have been described to induce synaptogenesis in principal neurons of the hippocampus and have been shown to be synthesized and released by exactly these neurons. Here, we have focused on the significance of local estrogen synthesis on spine synapse formation and the synthesis of synaptic proteins. To this end, we reduced hippocampal estrogen synthesis in vitro with letrozole, a reversible nonsteroidal aromatase inhibitor. In hippocampal slice cultures, letrozole treatment resulted in a dose-dependent decrease of 17beta-estradiol as quantified by RIA. This was accompanied by a significant decrease in the density of spine synapses and in the number of presynaptic boutons. Quantitative immunohistochemistry revealed a downregulation of spinophilin, a marker of dendritic spines, and synaptophysin, a protein of presynaptic vesicles, in response to letrozole. Surprisingly, no increase in the density of spines, boutons, and synapses and in spinophilin expression was seen after application of estradiol to the medium of cultures that had not been treated with letrozole. However, synaptophysin expression was upregulated under these conditions. Our results point to an essential role of endogenous hippocampal estrogen synthesis in...Continue Reading

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Mentioned in this Paper

Estrogen Biosynthetic Process
Immunohistochemistry
Aromatase Inhibitors
Neurons
Estradiol, (16 alpha,17 beta)-Isomer
Estradiol Measurement
Triazoles
Femara
Nerve Endings
Neuronal Plasticity

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