Prevention of age-related dysregulation of calcium dynamics by estrogen in neurons

To determine the impact of aging and 17 beta-estradiol on neuronal Ca2+ homeostasis, intracellular Fura-2 Ca2+-imaging was conducted during, 20-pulses of glutamate in hippocampal neurons Cultured front embryonic (E18). middle-age (10 months) and old (24 months) rat brain. Marked age-related differences in intracellular Ca2+ ([Ca2+]i) homeostasis and striking regulation by 17 beta-estradiol were seen. Embryonic neurons exhibited the greatest capacity to regulate Ca2+ homeostasis, followed by middle-age neurons. In old neurons. the first peak [Ca2+]i was substantially greater than at other ages and the return to baseline Ca2+ rapidly dysregulated with an inability to restore [Ca2+]i following the first glutamate Pulse which persisted throughout the 20 pulses. 17 beta-Estradiol pretreatment of old neurons profoundly attenuated the peak [Ca2+]i rise and delayed the age-associated dysregulation of baseline [Ca2+]i, normalizing responses to those of middle-age neurons treated with estradiol. The efficacy of 17 beta-estradiol extended below 10 pg/ml with full protection against toxicity front glutamate and A beta (1-40). These results demonstrate age-associated dysregulation of [Ca2+]i homeostasis which was largely prevented by 17 beta-estradiol with implications for estrogen/hormone therapy. (C) 2005 Elscvier Inc. All rights reserved.