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β‐Amyloid peptide induces ultrastructural changes in synaptosomes and potentiates mitochondrial dysfunction in the presence of ryanodine
Author(s) -
MungarroMenchaca Xavier,
Ferrera Patricia,
Morán Julio,
Arias Clorinda
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10193
Subject(s) - ryanodine receptor , synaptophysin , mitochondrion , neurodegeneration , synaptosome , microbiology and biotechnology , synaptic vesicle , neurotransmission , chemistry , biology , biochemistry , endoplasmic reticulum , medicine , vesicle , receptor , in vitro , immunohistochemistry , disease , membrane , immunology
In Alzheimer's disease (AD), loss of synapses exceeds neuronal loss and some evidence suggests a role of β‐amyloid protein (Aβ) in synaptic degeneration through a mechanism which may involve intraneuronal Ca 2+ dyshomeostasis. Emerging evidence points to the participation of the internal Ca 2+ stores in the pathophysiology of neurodegeneration in AD. To test the involvement of intrasynaptic Ca 2+ mobilization in Aβ toxicity, we explored the role of ryanodine receptor activation in rat cortical synaptosomes taken as a model system for the central presynapses. Evaluation of synaptosomal mitochondrial redox capacity was assessed by the MTT reduction technique, and ultrastructural changes of synaptosomes after exposure to Aβ and ryanodine were evaluated by electron microscopy. Our results show that Aβ potentiates mitochondrial dysfunction in the presence of ryanodine and induces morphological changes consisting of mitochondrial swelling and intense small synaptic vesicles depletion. These changes were accompanied by a reduction in the content of synaptophysin and actin proteins. The reduction of actin immunoreactivity was reversed in the presence of a wide range caspase inhibitors, suggesting the activation of synaptic apoptotic mechanisms. © 2002 Wiley‐Liss, Inc.