Onset of estrogen replacement has a critical effect on synaptic density of CA1 hippocampus in ovariectomized adult rats

Menopause. Sep-Oct 2003;10(5):406-11. doi: 10.1097/01.GME.0000064816.74043.E9.

Abstract

Objectives: The aim of this study was to evaluate differences between estrogen replacement therapy initiated either 4 or 12 days after ovariectomy on the synaptic density of the hippocampal CA1 field in rats.

Design: Female, adult, Wistar rats were ovariectomized bilaterally under ether anesthesia and divided among the following groups: 1) estrogen (conjugated equine estrogen 50 microg in 0.5 mL of propylene glycol, daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 5); 2) propylene glycol (0.5 mL daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 4); 3) estrogen (conjugated equine estrogen 50 microg in 0.5 mL of propylene glycol, daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3); 4) propylene glycol (0.5 mL daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3). At the end of the treatment, the rats were processed for electron microscopy and light analysis.

Results: Synaptic density in all of the CA1 strata subjected to evaluation was significantly higher in animals in which estrogen replacement was initiated 4 days after ovariectomy as compared with controls. In contrast, initiation of treatment after a 12-day interval did not result in recovery of synaptic density in any of the CA1 strata and was significantly lower than that of the animals subjected to hormone replacement after a 4-day delay (P < 0.01).

Conclusion: The delay for hormone replacement therapy might have critical implications for modulating synaptic density.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Estrogen Replacement Therapy*
  • Estrogens / pharmacology*
  • Estrogens, Conjugated (USP) / pharmacology*
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / ultrastructure
  • Ovariectomy
  • Rats
  • Rats, Wistar
  • Synapses / drug effects*
  • Synapses / ultrastructure
  • Time Factors

Substances

  • Estrogens
  • Estrogens, Conjugated (USP)