title: Estrogen protects against beta-amyloid-induced neurotoxicity in rat hippocampal neurons by activation of Akt.
abstract: 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 17beta-estradiol (E2) inhibition of beta-amyloid peptide (31-35) (Abeta31-35)-induced neurotoxicity in cultured rat hippocampal neurons. Abeta31-35 (25-30 betaM) 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 microM), a specific PI3-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.
authors: Behavioral Endocrinology Branch NIMH, Building 10, Room 3N238, NIH, Bethesda, MD 20892, USA.
authors: L
authors: L
authors: Zhang
authors: D R
authors: DR
authors: Rubinow
authors: G
authors: G
authors: Xaing
authors: B S
authors: BS
authors: Li
authors: Y H
authors: YH
authors: Chang
authors: D
authors: D
authors: Maric
authors: J L
authors: JL
authors: Barker
authors: W
authors: W
authors: Ma
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005333:Fetus; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D002867:Chromones; D004791:Enzyme Inhibitors; D004958:Estradiol; D004965:Estrogen Antagonists; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011960:Receptors, Estrogen; D013629:Tamoxifen; C113042:amyloid beta-protein (31-35); C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494920:Akt1 protein, rat