title: A beta 25-35 induces presynaptic changes in organotypic hippocampal slice cultures.
abstract: Memory loss in Alzheimer's disease (AD) may be related to synaptic defects in damaged hippocampal neurons. We investigated the relationship between amyloid peptide A beta 25-35-induced neuronal death pattern and presynaptic changes in organotypic hippocampal slice cultures. In propidium iodide (PI) uptake and annexin V labeling, A beta 25-35-induced neuronal damage dramatically increased in a concentration dependent manner, indicating both types of cell death. In ultrastructural analysis, apoptotic features in CA1 and CA3 area and synaptic disruption in stratum lucidum were detected in A beta 25-35-treated slices. Immunofluorescence and Western blot analysis for caspase-3 showed A beta 25-35 concentration dependently induced caspase-3 activation. Immunofluorescence and Western blot analysis to determine changes in presynaptic marker proteins demonstrated that expression of synaptosomal-associated protein-25 (SNAP-25) and synaptophysin were reduced by A beta 25-35 in CA1, CA3 and DG area at concentrations >2.5 microM. In conclusion, A beta 25-35-induced apoptotic cell death and caspase-3 activation at relatively low concentration, and induced synaptic disruption and loss of synaptic marker protein at concentrations >2.5 microM in organotypic hippocampal slice cultures. These suggest that A beta 25-35-induced apoptosis via triggering caspase-3 activation and lead to synaptic dysfunction in organotypic hippocampal slice cultures.
authors.affiliation: Department of Pharmacology, Medical Research Institute, School of Medicine, Ewha Womans University, 911-1, Mok-6-Dong, Yangcheon-Gu, Seoul, South Korea.
authors.forename: Eun Cheng
authors.initials: EC
authors.lastname: Suh
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Jung
authors.forename: Yul A
authors.initials: YA
authors.lastname: Kim
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Park
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016708:Synaptophysin / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017304:Annexin A5; D010446:Peptide Fragments; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; C074636:amyloid beta-protein (25-35); D053148:Caspase 3