β-Amyloid peptide induces ultrastructural changes in synaptosomes and potentiates mitochondrial dysfunction in the presence of ryanodine

✍ Scribed by Xavier Mungarro-Menchaca; Patricia Ferrera; Julio Morán; Clorinda Arias

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 261 KB
• Volume: 68
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.10193

✦ Synopsis

Abstract

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.