Effects of estradiol and DHEA on morphological synaptic plasticity

Abstract

Experimental data demonstrate that the nervous system is widely influenced by sex hormones, and the brain is continuously shaped by the environment via the changing hormone milieu throughout the entire life. The effects of gonadal hormones extend beyond regulating gonadotropin secretion; they are able to alter the structure of the adult nervous system by changing neuron and synapse numbers, as well as dendritic and synaptic morphology. These structural modifications are believed to serve as a morphological basis for varying behavior and cellular activity. In this review, we discuss the hormonally induced synaptic remodeling in different hypothalamic nuclei and in the hippocampus, focusing on specificity of action, time course, and functional consequences of synaptic alterations. It has been shown that the effect of estradiol is highly specific. In the arcuate nucleus, spine synapses and GABAergic axo-somatic terminals are affected, while in case of the hippocampus, estrogen induces the formation of spine synapses. Morphological and electrophysiological data show that synaptic remodeling could be very rapid. The neurosteroid dehydroepiandrosterone can also induce synaptic plasticity, reproducing the robust synaptogenic effect of estrogen. The underlying mechanisms, however, show considerable gender differences. Nevertheless, the many favorable responses to dehydroepiandrosterone by the brain and the periphery make this neurosteroid a promising substitute for estrogen in hormone therapy. © 2008 Springer Netherlands.