Estrogen protects against β-amyloid-induced neurotoxicity in rat hippocampal neurons by activation of Akt

The cellular mechanisms underlying the neuroprotective effects of estrogen are only beginning to be elucidated. Here we examined the role of protein kinase B (Akt) activation in 17β-estradiol (E2) inhibition of β-amyloid peptide (31-35) (Aβ_31-35)-induced neurotoxicity in cultured rat hippocampal neurons. Aβ_31-35 (25-30 βM) significantly decreased the total number of microtubule associated protein-2 positive cells (MAP2⁺). This decrease was significantly reversed by pre-treatment with 100 nM E2. Further, 100 nM E2 alone significantly increased the total number of protein kinase B and microtubule associated protein-2 positive cells compared with controls. Such E2-induced increases were inhibited by. LY294002 (20 μM), a specific P13-K inhibitor, as well as by tamoxifen, an estrogen receptor antagonist/selective estrogen receptor modulator. These results indicate that the neuroprotective effects of E2 may be mediated at least in part via estrogen receptor-mediated protein kinase B activation.