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Related Experiment Videos

Do apoptotic mechanisms regulate synaptic plasticity and growth-cone motility?

Charles P Gilman1, Mark P Mattson

  • 1Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA.

Neuromolecular Medicine
|November 14, 2002
PubMed
Summary
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Programmed cell death pathways, known as apoptosis, locally influence neuronal growth cone and synapse function. These apoptotic signaling mechanisms are key regulators of neuronal plasticity and development.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Synaptic signaling pathways, involving receptors and kinase cascades, control neuronal communication and development.
  • These pathways are also present in growth cones, guiding neuronal pathfinding and synapse formation.
  • While known to affect neuronal survival via apoptosis, the local impact of apoptotic cascades on growth cones and synapses was unexplored.

Purpose of the Study:

  • To investigate the local actions of apoptotic biochemical cascades on the function and structural dynamics of neuronal growth cones and synapses.
  • To identify novel apoptotic and anti-apoptotic signaling mechanisms regulating synaptic and developmental plasticity.
  • To explore the role of apoptosis in neuronal plasticity under physiological conditions.

Main Methods:

Related Experiment Videos

  • Review of existing literature on apoptotic cascades and neuronal signaling.
  • Presentation of experimental findings from the authors' laboratory.
  • Analysis of signaling pathways involving caspases, Par-4, p53, neurotrophic factors, and NF-kappaB.

Main Results:

  • Apoptotic synaptic cascades, including caspase activation, can cleave ionotropic glutamate-receptor subunits, modifying synaptic plasticity.
  • Caspases can cleave cytoskeletal proteins in growth cones, regulating neurite outgrowth.
  • Pro-apoptotic proteins (Par-4, p53) and anti-apoptotic signals (neurotrophic factors, NF-kappaB) modulate synaptic and developmental plasticity.

Conclusions:

  • Apoptotic signaling mechanisms play a direct, local role in regulating the structural and functional plasticity of neuronal growth cones and synapses.
  • These pathways are integral to both neuronal development and ongoing neuronal circuit function.
  • The study highlights a dual role for apoptosis-related signaling in neuronal plasticity.