Estrogen and Brain Function: Implications for Aging and Dementia

Estrogen is involved in a multitude of processes throughout the lifespan in the brains of both females and males. For example, this steroid hormone affects critical developmental events such as neuronal differentiation, growth and synaptogenesis, which ultimately leads to the establishment of the sexually differentiated brain (McEwen et al. 1977; Maclusky et al. 1987; Toaran Allerland 1991). In the adult CNS, estrogen, together with progesterone, orchestrate rapid and continuous neuroplastic events, including the cyclic synaptic turnover which occurs throughout the rat estrus cycle (Wooley and McEwen, 1993). The aging brain is associated with declines in many neural systems, often resulting in functional deficits; recent evidence suggests that estrogen replacement can decrease the risk of neurodegenerative disorders, such as Alzheimer's disease, and alleviate some of the cognitive deficits in afflicted women (Paganin-Hill and Henderson 1994;Henderson et al. 1994; Tang et al. 1996). Considering these few examples, it becomes apparent that the brain systems targeted by estrogen are many, encompassing both reproductive and non-reproductive circuitries. In this chapter, we will review evidence for estrogen regulation of specific brain-cell phenotypes in an attempt to understand estrogen's influence on brain function. First, we will briefly consider the various means by which estrogen is believed to interact with target cells.