25-35 induces presynaptic changes in organotypic hippocampal slice cultures

Eun Cheng Suh, Yeon Joo Jung, Yul A. Kim, Eun Mi Park, Kyung Eun Lee

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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 Aβ25-35-induced neuronal death pattern and presynaptic changes in organotypic hippocampal slice cultures. In propidium iodide (PI) uptake and annexin V labeling, Aβ25-35-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 Aβ25-35-treated slices. Immunofluorescence and Western blot analysis for caspase-3 showed Aβ25-35 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 Aβ25-35 in CA1, CA3 and DG area at concentrations >2.5 μM. In conclusion, Aβ25-35-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 μM in organotypic hippocampal slice cultures. These suggest that Aβ25-35-induced apoptosis via triggering caspase-3 activation and lead to synaptic dysfunction in organotypic hippocampal slice cultures.

Original languageEnglish
Pages (from-to)691-699
Number of pages9
JournalNeuroToxicology
Volume29
Issue number4
DOIs
StatePublished - Jul 2008

Bibliographical note

Funding Information:
This work was supported by the Korea Research Foundation Grant funded from the Korean Government (No. R04-2004-000-10019-0).

Keywords

  • Apoptosis
  • Organotypic hippocampal slice culture
  • Presynaptic dysfunction

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