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Related Experiment Videos

Evidence for synaptic apoptosis

M P Mattson1, J N Keller, J G Begley

  • 1Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA.

Experimental Neurology
|September 23, 1998
PubMed
Summary
This summary is machine-generated.

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Neurons initiate apoptosis locally at synapses, not just the cell body. This localized cell death process, involving caspases, may contribute to neurodegenerative disorders.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Neurons undergo apoptosis, a programmed cell death, in various conditions.
  • Neuronal morphology with extensive neuritic arbors suggests localized death signaling.
  • Glutamate receptor overactivation is linked to neurodegeneration.

Purpose of the Study:

  • To investigate if apoptotic biochemical changes occur locally in neuronal synapses.
  • To determine if synapses can generate signals that induce apoptosis.
  • To explore the role of local apoptotic signaling in neurodegenerative diseases.

Main Methods:

  • Cortical synaptosomes were exposed to staurosporine and Fe2+.
  • Cultured hippocampal neurons were treated with staurosporine and glutamate.

Related Experiment Videos

  • Caspase activation, mitochondrial function, and nuclear apoptosis signals were assessed.
  • Caspase inhibitor zVAD-fmk was used to block apoptosis.

    • Main Results:

    • Synaptosomes showed apoptosis markers like loss of phospholipid asymmetry, caspase activation, and mitochondrial dysfunction.
    • Cytosolic extracts from insulted synaptosomes induced nuclear apoptosis.
    • Cultured neurons exhibited local caspase activation and mitochondrial depolarization in dendrites upon glutamate exposure.
    • zVAD-fmk inhibited these apoptotic events.

    Conclusions:

    • Apoptotic biochemical cascades are activated locally within synapses and dendrites.
    • Synapses can generate signals that trigger apoptosis.
    • Local apoptotic signaling may play a role in synapse loss and neuronal death in neurodegenerative disorders involving glutamate excitotoxicity.