Figure 7. Loss of nongenomic signaling and neuroprotective actions of E2 in the hippocampus following long-term E2 deprivation.

(A) NeuN (red) and Fluoro-Jade B (green) staining results in hippocampal CA1 of long-term E2 deprived animals treated with E2 or Placebo (Pla). Note that E2 loses its ability to protect CA1 neurons against ischemic damage after long-term E2 deprivation. (B) Effect of long term E2 deprivation on nongenomic signaling by E2. Hippocampal CA1 protein lysate samples at 3 h reperfusion from immediate (Imm) and 10-week later (10W) E2-replaced rats were analyzed by Western blot for p-Akt and Akt levels (a). (b) Samples were IP with anti-ERα antibody and blotted with anti-P85 subunit of PI3K. An equal amount of protein was also Western blotted with anti-P85 to examine total protein expression. *P < 0.05 vs. Pla and 10-week E2 groups. (C) NeuN (red) and Fluoro-Jade B (green) staining reveals that EDC neuroprotection is lost in 10W animals. (D) EDC loses ability to activate Akt after 10-week E2 deprivation. *P < 0.05 vs. vehicle and 10-week EDC groups. n.s: no significant difference. (E) In contrast to loss of E2 neural actions after long-term E2 deprivation, the trophic effect of E2 on the uterus is not lost following 10-week E2 deprivation. Scale bar, 1 cm; 1×. Reprinted, with permission, from Journal of Neuroscience [203].