Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood

TLDR

Gonadal steroids influence hippocampal physiology, yet it is unknown whether they affect neuronal morphology in the adult intact rat hippocampus. The study aimed to determine whether female sex hormones alter hippocampal morphology in adult rats. Golgi impregnation was performed on ovariectomized rats with or without estradiol or estradiol plus progesterone replacement. Ovariectomy markedly reduced dendritic spine density in CA1 pyramidal cells, an effect prevented by estradiol and enhanced by progesterone within hours, while CA3 and dentate cells were unaffected, indicating gonadal steroids are essential for maintaining normal CA1 structure and that spine density may fluctuate during the estrous cycle.

Abstract

Gonadal steroids are known to influence hippocampal physiology in adulthood. It is presently unknown whether gonadal steroids influence the morphology of hippocampal neurons in the adult intact rat brain. In order to determine whether female sex hormones influence hippocampal morphology in the intact adult, we performed Golgi impregnation on brains from ovariectomized rats and ovariectomized rats which received estradiol or estradiol and progesterone replacement. Removal of circulating gonadal steroids by ovariectomy of adult female rats resulted in a profound decrease in dendritic spine density in CA1 pyramidal cells of the hippocampus. Estradiol replacement prevented the observed decrease in dendritic spine density; progesterone augmented the effect of estradiol within a short time period (5 hr). Ovariectomy or gonadal steroid replacement did not affect spine density of CA3 pyramidal cells or granule cells of the dentate gyrus. These results demonstrate that gonadal steroids are necessary for the maintenance of normal adult CA1 hippocampal pyramidal cell structure. The short time course required to observe these effects (3 d for the estradiol effect and 5 hr for the progesterone effect) implies that CA1 pyramidal cell dendritic spine density may fluctuate during the normal (4-5 d) rat estrous cycle.