title: Reduction in Aβ-induced cell death in the hippocampus of 17β-estradiol-treated female rats is associated with an increase in IGF-I signaling and somatostatinergic tone.
abstract: Several studies indicate that 17β-estradiol (E2) protects against amyloid β-peptide (Aβ)-induced cell death and activates factors associated with learning and memory, a function involving the hippocampal somatostatinergic system. As alterations in somatostatin have been demonstrated in Alzheimer's disease, we examined whether E2 prevents changes in the hippocampal somatostatinergic system induced by Aβ25-35 and cell death, as well as the possible involvement of leptin and insulin-like growth factor (IGF)-I signaling. We also measured the levels of Aβ proteases neprilysin and insulin-degrading-enzyme. Co-administration of E2 with Aβ25-35 reduced both its levels and cell death, in addition to preventing the Aβ-induced depletion of some somatostatinergic parameters. Activation of leptin and IGF-I pathways increased after E2 co-administration, and this correlated with changes in the somatostatinergic system. Changes in some components of this system were inversely related with Aβ levels and cell death. Moreover, neprilysin levels were increased only in Aβ plus E2-treated rats and E2 prevented the Aβ-induced insulin-degrading-enzyme reduction. Our results suggest that the E2-induced reduction in cell death is related to lower Aβ levels, probably because of IGF-I and somatostatin modulation of Aβ proteases. We asked how 17β-estradiol (E2) protects against β-amyloid (Aβ)-induced cell death. E2 co-administration prevents Aβ-produced depletion of hippocampal somatostatin (SRIF) by an IGF-I-mediated mechanism, being related this protective effect with an increase in Aβ proteases. Our results suggest that the E2-induced reduction in cell death is related to lower Aβ levels, probably because of SRIF modulation of Aβ proteases. CREB, cAMP response element-binding protein; IGF-I, insulin-like growth factor-I; STAT3, signal transducer and activator of transcription-3.
authors.affiliation: Neurobiochemistry Group, Unit of Biochemistry and Molecular Biology, Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares, Spain.
authors.forename: Aránzazu
authors.initials: A
authors.lastname: Perianes-Cachero
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Canelles
authors.affiliation: Neurobiochemistry Group, Unit of Biochemistry and Molecular Biology, Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Aguado-Llera
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Frago
authors.affiliation: Department of Biomedicine and Biotechnology, Universidad de Alcalá, Alcalá de Henares and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Madrid, Spain.
authors.forename: María Val
authors.initials: MV
authors.lastname: Toledo-Lobo
authors.affiliation: Department of Neuroscience, EuroEspes Biotechnology, Polígono de Bergondo, A Coruña, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Carrera
authors.affiliation: EuroEspes Biomedical Research Center, Institute for CNS Disorders and Chair of Genomic Medicine, University of Camilo José Cela, Villanueva de la Cañada, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Cacabelos
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
authors.affiliation: Neurobiochemistry Group, Unit of Biochemistry and Molecular Biology, Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arilla-Ferreiro
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Barrios
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013004:Somatostatin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017481:Receptors, Somatostatin; D004958:Estradiol; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I
keywords: Alzheimer′s disease; IGF-I signaling; Neprilysin; estradiol; somatostatin; β-amyloid