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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 T, Kaneko N, Zukin RS, Castillo PE, Etgen AM - PLoS ONE (2012)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America.

ABSTRACT

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.

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.

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CA1 synapses in the aging hippocampus retain responsiveness to E2 after long-term hormone deprivation.Evoked fEPSPs were measured in acute hippocampal slices from aged (15–18 mo, 6 months after OVX) and young (2 mo, 7–10 days after OVX) females. E2 (1 nM) was bath applied after 15 min stable baseline. Panel A: E2 facilitated fEPSPs in young (open circles) and aged (black circles) females with short latency. Panel B: Representative fEPSPs from young (n = 7 slices from 6 rats) and aged (n = 5 slices from 4 rats) rats before and after E2 application. Panel C: The averaged responses for the last 5 min baseline recording and the averaged responses during 25–30 min after the start of E2 application. Data are means ± SEM. n.s., not significant. **, p<0.01.
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pone-0038018-g004: CA1 synapses in the aging hippocampus retain responsiveness to E2 after long-term hormone deprivation.Evoked fEPSPs were measured in acute hippocampal slices from aged (15–18 mo, 6 months after OVX) and young (2 mo, 7–10 days after OVX) females. E2 (1 nM) was bath applied after 15 min stable baseline. Panel A: E2 facilitated fEPSPs in young (open circles) and aged (black circles) females with short latency. Panel B: Representative fEPSPs from young (n = 7 slices from 6 rats) and aged (n = 5 slices from 4 rats) rats before and after E2 application. Panel C: The averaged responses for the last 5 min baseline recording and the averaged responses during 25–30 min after the start of E2 application. Data are means ± SEM. n.s., not significant. **, p<0.01.

Mentions: We recorded fEPSPs at CA3-CA1 synapses elicited by Schaffer collateral stimulation in acute hippocampal slices prepared from aged (15–18 mo, 6 months after OVX) and young adult (2 mo, 7–10 days after OVX) females. Bath application of E2 (1 nM) significantly enhanced synaptic responses (F = 43.1, p<0.001, Fig.4) in slices from both young (110.2±1.0% of baseline, 7 slices from 6 animals, p<0.01 vs. baseline) and aged (109.1±2.4% of baseline, 5 slices from 4 animals, p<0.01 vs. baseline) OVX rats with a similar latency (approximately 5–7 min) and magnitude measured 25–30 min after the start of E2 application.


Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.

Inagaki T, Kaneko N, Zukin RS, Castillo PE, Etgen AM - PLoS ONE (2012)

CA1 synapses in the aging hippocampus retain responsiveness to E2 after long-term hormone deprivation.Evoked fEPSPs were measured in acute hippocampal slices from aged (15–18 mo, 6 months after OVX) and young (2 mo, 7–10 days after OVX) females. E2 (1 nM) was bath applied after 15 min stable baseline. Panel A: E2 facilitated fEPSPs in young (open circles) and aged (black circles) females with short latency. Panel B: Representative fEPSPs from young (n = 7 slices from 6 rats) and aged (n = 5 slices from 4 rats) rats before and after E2 application. Panel C: The averaged responses for the last 5 min baseline recording and the averaged responses during 25–30 min after the start of E2 application. Data are means ± SEM. n.s., not significant. **, p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3366987&req=5

pone-0038018-g004: CA1 synapses in the aging hippocampus retain responsiveness to E2 after long-term hormone deprivation.Evoked fEPSPs were measured in acute hippocampal slices from aged (15–18 mo, 6 months after OVX) and young (2 mo, 7–10 days after OVX) females. E2 (1 nM) was bath applied after 15 min stable baseline. Panel A: E2 facilitated fEPSPs in young (open circles) and aged (black circles) females with short latency. Panel B: Representative fEPSPs from young (n = 7 slices from 6 rats) and aged (n = 5 slices from 4 rats) rats before and after E2 application. Panel C: The averaged responses for the last 5 min baseline recording and the averaged responses during 25–30 min after the start of E2 application. Data are means ± SEM. n.s., not significant. **, p<0.01.
Mentions: We recorded fEPSPs at CA3-CA1 synapses elicited by Schaffer collateral stimulation in acute hippocampal slices prepared from aged (15–18 mo, 6 months after OVX) and young adult (2 mo, 7–10 days after OVX) females. Bath application of E2 (1 nM) significantly enhanced synaptic responses (F = 43.1, p<0.001, Fig.4) in slices from both young (110.2±1.0% of baseline, 7 slices from 6 animals, p<0.01 vs. baseline) and aged (109.1±2.4% of baseline, 5 slices from 4 animals, p<0.01 vs. baseline) OVX rats with a similar latency (approximately 5–7 min) and magnitude measured 25–30 min after the start of E2 application.

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America.

ABSTRACT

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.

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.

Show MeSH
Related in: MedlinePlus