Pathological remodeling of dendritic spines

John N. Campbell, Jonathon E. Kurz, Severn B. Churn*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations

Abstract

As highly plastic structures that receive most of the excitatory signaling in the brain, dendritic spines are particularly vulnerable to excitotoxic injury. Excessive stimulation of the dendritic spine can dramatically and persistently restructure the post-synapse. There appear to be multiple, complementary mechanisms which ultimately remodel and potentially destabilize the dendritic spine. Activation of these mechanisms is linked to the excitotoxic influx of calcium through post-synaptic receptor- and/or voltage-gated ion channels. The calcium-activated phosphatase, calcineurin, mediates at least two spinedestabilizing mechanisms: activation of the actin regulatory protein, cofilin, which binds and disrupts cytoskeletal actin; and a downstream increase in mRNA expression of Snk (serum induced kinase), which targets for destruction a cytoskeletal-stabilizing protein, SPAR (spine-associated Rap guanosine triphosphatase activating protein). The excitotoxic influx of calcium also triggers proteolysis of another cytoskeletal-stabilizing protein, MARCKS (myristoylated alanine-rich C-kinase substrate). The remodeling accomplished by these mechanisms has multiple functional consequences from acute protective effects to pathological re-wiring of neuronal circuitry. Injury-induced alterations of neural circuitry are thought to explain the development of post-injury neurological pathologies such as epilepsy. Therefore, stabilizing dendritic spines and other components of neural circuitry against injury-induced alterations may be a novel approach to preventing post-injury neurologic pathology.

Original languageEnglish (US)
Title of host publicationDendritic Spines
Subtitle of host publicationBiochemistry, Modeling and Properties
PublisherNova Science Publishers, Inc.
Pages45-65
Number of pages21
ISBN (Print)9781607414605
StatePublished - Apr 1 2009

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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