Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.
BACKGROUND
Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17β-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.


RESULTS
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
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.
Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Tomoko
T
Inagaki
Naoki
N
Kaneko
R Suzanne
RS
Zukin
Pablo E
PE
Castillo
Anne M
AM
Etgen
D000375:Aging / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D018696:Neuroprotective Agents; D004958:Estradiol