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Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.
Inagaki, Tomoko; Kaneko, Naoki; Zukin, R Suzanne; Castillo, Pablo E; Etgen, Anne M.
Affiliation
  • Inagaki T; Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America.
PLoS One ; 7(6): e38018, 2012.
Article in En | MEDLINE | ID: mdl-22675505
ABSTRACT

BACKGROUND:

Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17ß-estradiol (E2) reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia. METHODOLOGY/PRINCIPAL

FINDINGS:

The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months) after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 µg) infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non-ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP) was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats. CONCLUSIONS/

SIGNIFICANCE:

The data demonstrate that 1) acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2) E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after prolonged periods of hormone withdrawal.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aging / Ovariectomy / Brain Ischemia / Synaptic Transmission / Estradiol / Hippocampus / Neurons Limits: Animals Language: En Journal: PLoS One Journal subject: CIENCIA / MEDICINA Year: 2012 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aging / Ovariectomy / Brain Ischemia / Synaptic Transmission / Estradiol / Hippocampus / Neurons Limits: Animals Language: En Journal: PLoS One Journal subject: CIENCIA / MEDICINA Year: 2012 Document type: Article Affiliation country: United States