Estradiol: a hormone with diverse and contradictory neuroprotective actions

Figures & data

Figure 1. Overview of the brain cell types and neuromodulators influenced by estrogens. The ability of estrogens to exert trophic and protective actions depends upon their ability to alter the birth and death of neurons, synaptogenesis, and neuritogenesis. Estradiol influences neurons, astrocytes, and microglia through altering the expression of a broad profile of neurotransmitters and neuropeptides and their receptors, pro- and anti-inflammatory agents, and factors which influence, birth, survival, growth, and maturation of neurons.

Figure 2. Estradiol influences the number of newborn neurons. Panel A shows confocal micrographs of newborn neurons dual-labeled with bromodeoxyuridine and doublecortin in vehicle and estradiol-treated mice following stroke injury. Panel B shows the mean of groups of 4 to 6 animals in each experimental group and shows that the differences are statistically significant.

Figure 3. Estradiol protects the brain only if treatment is initiated immediately after hypoestrogenicity is induced. Estradiol decreases the size of the infarct, induces estrogen receptor (ER) and suppresses inflammation only if it is administered immediately after ovariectomy. We have used ovariectomy to mimic the menopause. These findings strongly suggest that, if estrogen therapy (ET) is initiated after several years of postmenopause, as was the case in the Womens' Health Initiative, that ET will not be effective in protecting the brain against neurodegeneration.