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 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.
Zhang
L
L
Behavioral Endocrinology Branch NIMH, Building 10, Room 3N238, NIH, Bethesda, MD 20892, USA.
Rubinow
D R
DR
Xaing
G
G
Li
B S
BS
Chang
Y H
YH
Maric
D
D
Barker
J L
JL
Ma
W
W
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
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