Figure 7.

Estradiol enhances excitation; estradiol dampens excitation. The neuroprotective versus neurodamaging effects of estradiol can both be traced to the impact of the steroid on intracellular free calcium. A, Pretreatment with estradiol reduces the percentage of glutamate-induced calcium in cultured hippocampal neurons by ~30%. A pseudo-colored image shows the relative amount of calcium after glutamate in neurons treated with vehicle (top) versus neurons treated with physiological levels of estradiol for 24 to 48 h prior (reprinted with permission from Hilton and others 2006). B, Activation of GABA-A receptors in immature hippocampal neurons also invokes calcium influx and prior treatment of neurons with the same estradiol regimen markedly enhances the amount of calcium as well as the number of neurons that respond to GABA with membrane depolarization. The top panel shows a representative trace (blue bar equals muscimol application, a GABA-A agonist) and the bottom panel is pseudo-colored images showing calcium responses across time (reprinted from Nunez and others 2005, European Journal of Neuroscience, with permission from Wiley-Blackwell.).