Estrogen protects against beta-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 k inase B (Akt) activation in 17 beta -estradiol (E2) inhibition of beta -amy loid peptide (31-35) (A beta (31-35))induced neurotoxicity in cultured rat hippocampal neurons. A beta (31-35) (25-30 betaM) significantly decreased t he 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 prot ein kinase B and microtubule associated protein-2 positive cells compared w ith controls. Such E2-induced increases were inhibited by LY294002 (20 muM) , a specific P13-K inhibitor, as well as by tamoxifen, an estrogen receptor antagonist/selective estrogen receptor modulator. These results indicate t hat the neuroprotective effects of E2 may be mediated at least in part via estrogen receptor-mediated protein kinase B activation. NeuroReport 12:1919 -1923 (C) 2001 Lippinicott Williams & Wilkins.