title: Early β-Amyloid-induced Synaptic Dysfunction Is Counteracted by Estrogen in Organotypic Hippocampal Cultures.
abstract: In the present study we set up a model of slow progression of neuronal injury by exposing organotypic hippocampal cultures to a low concentration of Amyloid β (25-35) peptide (Aβ, 2 μM) to analyze the time-related effects of 17-β estradiol (17β-E2, 10 nM). Neuronal death occurs after 7 d and is prevented by addition of 17β-E2 24 h prior to, together with or 48 h after exposure to Aβ. This effect is mimicked by selective ERα agonist PPT (100 nM). Treatment with Aβ leads to early and transient (16-72 h) increase of pre- and post-synaptic proteins synaptophysin and PSD95, followed by a decrease coincident with neuronal death (7d), all prevented by 17β-E2. At 72 h of Aβ exposure, synaptic activity is increased, as by higher levels of glutamate and increased loading and unloading of FM 1-43-labeled synaptic vesicles. All these effects are also prevented by 17β-E2. These data point out beneficial effects of estrogen on early Aβ-induced synaptic disruption.
authors.forename: Sara
authors.initials: S
authors.lastname: Merlo
authors.forename: Simona Federica
authors.initials: SF
authors.lastname: Spampinato
authors.forename: Francisco
authors.initials: F
authors.lastname: Capani
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, School of Medicine, Via S. Sofia 64, 95125 Catania, Italy. msortino@unict.it.
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Sortino
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D010636:Phenols / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D016229:Amyloid beta-Peptides; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010636:Phenols; D011720:Pyrazoles; C074636:amyloid beta-protein (25-35); C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D018698:Glutamic Acid; D004958:Estradiol