Estrogen up-regulates estrogen receptor α and synaptophysin in slice cultures of rat hippocampus

G. M. Rune, U. Wehrenberg, J. Prange-Kiel, L. Zhou, G. Adelmann, M. Frotscher

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


Previous studies have shown that estrogen application increases the density of synaptic input and the number of spines on CA1 pyramidal neurons. Here, we have investigated whether Schaffer collaterals to CA1 pyramidal cells are involved in this estrogen-induced synaptogenesis on CA1 pyramidal neurons. To this end, we studied estrogen-induced expression of both estrogen receptor (ER) subtypes (ERα and ERβ) together with the presynaptic marker synaptophysin in the rat hippocampus. In tissue sections as well as in slice cultures mRNA expression of ERα, ERβ and synaptophysin was higher in CA3 than in CA1, and mRNA expression and immunoreactivity for both ER subtypes were found in both principal cells and interneurons. By using quantitative image analysis we found stronger nuclear immunoreactivity for ERα in CA3 than in CA1. In slice cultures, supplementation of the medium with 10-8 M estradiol led to an increase of nuclear immunoreactivity for ERα, but not for ERβ, which was accompanied by a dramatic up-regulation of synaptophysin immunoreactivity in stratum radiatum of CA1. Together these findings indicate that estrogen effects on hippocampal neurons are more pronounced in CA3 than in CA1 and that ER activation in CA3 neurons leads to an up-regulation of a presynaptic marker protein in the axons of these cells, the Schaffer collaterals. We conclude that estradiol-induced spine formation on CA1 pyramidal cells may be mediated presynaptically, very likely by activation of ERα in CA3 pyramidal cells, followed by an increase in Schaffer collateral synapses.

Original languageEnglish (US)
Pages (from-to)167-175
Number of pages9
Issue number1
StatePublished - Aug 2 2002


  • Hippocampal circuitry
  • Schaffer collaterals
  • Slice culture
  • Steroid receptor
  • Synaptic plasticity
  • Synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)


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