Prevention of age-related dysregulation of calcium dynamics by estrogen in neurons
Prevention of age-related dysregulation of calcium dynamics by estrogen in neurons
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DOI：
10.1016/j.neurobiolaging.2005.01.019
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发表时间：
2006-02-01
影响因子：
4.2
通讯作者：
Brinton, RD
中科院分区：
文献类型：
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作者：
Brewer, GJ;Reichensperger, JD;Brinton, RD
为了确定衰老和17 β -雌二醇对神经元Ca2+稳态的影响，在培养前胚胎（E18）的海马神经元中，在20脉冲谷氨酸期间进行细胞内Fura-2 Ca2+成像。中年（10个月）和老年（24个月）大鼠脑。细胞内Ca2+ ([Ca2+]i)稳态和17 β -雌二醇显著调节的年龄相关差异被观察到。胚胎神经元调节Ca2+稳态的能力最强，其次是中年神经元。在老的神经元中。第一个峰值[Ca2+]i明显高于其他年龄，并且在第一个谷氨酸脉冲持续20个脉冲后，Ca2+迅速失调，无法恢复[Ca2+]i。17 β -雌二醇预处理老年神经元显著减弱了[Ca2+]i的峰值升高，延缓了与年龄相关的基线[Ca2+]i的失调，使中年神经元的反应与雌二醇处理的反应正常化。17 β -雌二醇的效力低于10 pg/ml，对谷氨酸和A β的毒性有充分的保护（1-40）。这些结果表明，年龄相关的[Ca2+]i稳态失调在很大程度上是由17 - β -雌二醇预防的，这对雌激素/激素治疗具有重要意义。(C) 2005 Elscvier Inc.版权所有。
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.