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beta-Amyloid peptide induces ultrastructural changes in synaptosomes and potentiates mitochondrial dysfunction in the

Xavier Mungarro-Menchaca1, Patricia Ferrera, Julio Morán

  • 1Departamento de Biología Celular y Fisiologia, Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México, D.F.

Journal of Neuroscience Research
|April 5, 2002
PubMed

Insights

Beta-amyloid protein (Abeta) exacerbates mitochondrial dysfunction in Alzheimer's disease (AD) synaptosomes. Ryanodine receptor activation and Abeta trigger synaptic vesicle depletion and apoptosis, highlighting a role for intracellular calcium stores in AD synaptic degeneration.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Synaptic loss in Alzheimer's disease (AD) is a key pathological feature.
  • Beta-amyloid protein (Abeta) is implicated in synaptic degeneration.
  • Intracellular calcium (Ca2+) dyshomeostasis may contribute to AD pathophysiology.

Purpose of the Study:

  • To investigate the role of intrasynaptic Ca2+ mobilization in Abeta toxicity.
  • To explore the involvement of ryanodine receptor activation in synaptic degeneration in AD models.

Main Methods:

  • Utilized rat cortical synaptosomes as a model for central presynapses.
  • Assessed mitochondrial redox capacity using the MTT reduction technique.
  • Evaluated ultrastructural changes via electron microscopy after exposure to Abeta and ryanodine.

Main Results:

  • Abeta potentiated mitochondrial dysfunction in the presence of ryanodine.
  • Observed synaptosome morphological changes: mitochondrial swelling and synaptic vesicle depletion.
  • Reduced levels of synaptophysin and actin proteins were noted.
  • Caspase inhibitors reversed actin reduction, suggesting synaptic apoptosis.

Conclusions:

  • Ryanodine receptor activation contributes to Abeta-induced synaptic damage.
  • Intrasynaptic Ca2+ release and mitochondrial dysfunction are critical in AD synaptic pathology.
  • Synaptic apoptosis, mediated by caspase activation, is involved in Abeta toxicity.

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