Prevention of age-related dysregulation of calcium dynamics by estrogen in neurons.
To determine the impact of aging and 17beta-estradiol on neuronal Ca2+ homeostasis, intracellular Fura-2 Ca2+-imaging was conducted during 20-pulses of glutamate in hippocampal neurons cultured from 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 17beta-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. 17beta-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 17beta-estradiol extended below 10 pg/ml with full protection against toxicity from glutamate and Abeta (1-40). These results demonstrate age-associated dysregulation of [Ca2+]i homeostasis which was largely prevented by 17beta-estradiol with implications for estrogen/hormone therapy.
Brewer
Gregory J
GJ
Department of Neurology, Southern Illinois University School Medicine, P.O. Box 19626, Springfield, IL 62794-9626, USA. gbrewer@siumed.edu
Reichensperger
Joel D
JD
Brinton
Roberta D
RD
D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004958:Estradiol / Q000494:pharmacology*; D016257:Fura-2; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D016229:Amyloid beta-Peptides; D018698:Glutamic Acid; D004958:Estradiol; D002118:Calcium; D016257:Fura-2