Culture models for the study of estradiol-induced synaptic plasticity

Estrogen, which classically affects areas of the brain related to reproduct ion, has also been found to affect brain regions important in learning and memory. Additionally, it has been suggested that estrogen exerts protective effects against neurodegenerative diseases such as Alzheimer's disease. Im portant mechanisms by which estrogen may confer protection are through the maintenance or modulation of existing synapses, or by the production of new ones. It has now been demonstrated that estrogen can increase synaptogenes is and spine production in the hippocampus, both in vivo as well as in prim ary hippocampal neurons in culture. The latter model system is the primary focus of this review. Synaptogenesis and spine production have been well ch aracterized in developing and adult animals, and parallels between the syna ptic morphology reflecting these processes can be readily observed in high- density primary hippocampal cultures. Moreover, in culture, estrogen induce s a variety of ultra structural modifications, many of which occur in vivo, that have been linked to various in vivo models of learning and memory. Fo r these reasons, high-density hippocampal culture systems should be regarde d as valuable tools with which to predict in vivo physiology, and may well be particularly useful for studies of the neuroprotective effects of estrog en.