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

Gregory J. Brewer, Joel D. Reichensperger, Roberta D. Brinton

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

To determine the impact of aging and 17β-estradiol on neuronal Ca 2+ 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 17β-estradiol were seen. Embryonic neurons exhibited the greatest capacity to regulate Ca2+ homeostasis followed by middle-age neurons. In old neurons, the first peak [Ca 2+]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. 17β-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 17β-estradiol extended below 10 pg/ml with full protection against toxicity from glutamate and Aβ (1-40). These results demonstrate age-associated dysregulation of [Ca2+]i homeostasis which was largely prevented by 17β-estradiol with implications for estrogen/hormone therapy.

Original languageEnglish (US)
Pages (from-to)306-317
Number of pages12
JournalNeurobiology of Aging
Volume27
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

Keywords

  • Aging
  • Calcium homeostasis
  • Estrogen
  • Glutamate toxicity
  • Neuroprotection
  • β-Amyloid toxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

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