Calpain activation contributes to dendritic remodeling after brief excitotoxic injury in vitro

Brian T. Faddis, M. Josh Hasbani, Mark P. Goldberg

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

The calcium-dependent protease calpain may contribute to neuronal death in acute neurological insults and may be activated very early in the neuronal injury cascade. We assessed the role of calpain in a model of rapid, reversible dendritic injury in murine cortical cultures. Brief sublethal NMDA exposure (1030 μM for 10 min) resulted in focal swellings, or varicosities, along the length of neuronal dendrites as visualized with the lipophilic membrane tracer Dil or with immunostaining using antibodies to the somatodendritic protein MAP2. These varicosities appeared within minutes of NMDA exposure and recovered spontaneously within 2 hr after NMDA removal. Addition of the calpain inhibitors MDL28, 170, calpain inhibitors I and II, and leupeptin (all 1-100 μM) had little effect on the development of NMDA- induced dendrite injury. However, the resolution of varicosities was substantially delayed by addition of calpain inhibitors after sublethal excitotoxic exposure. Using Western blots and immunocytochemistry, we observed reactivity for a calpain-specific spectrin proteolytic fragment during the period of recovery from dendritic swelling, but not during its format on. Spectrin breakdown product immunoreactivity could be blocked by the calpain inhibitor MDL28, 170 and appeared in neuronal cell bodies and neurites in a time course that paralleled dendritic recovery. These observations suggest hat calcium-dependent proteolysis contributes to recovery of cendritic structure after NMDA exposure. Calpain activation is not necessarily detrimental and may play a role in dendritic remodeling after neuronal injury.

Original languageEnglish (US)
Pages (from-to)951-959
Number of pages9
JournalJournal of Neuroscience
Volume17
Issue number3
StatePublished - 1997

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Neuronal Plasticity
Calpain
N-Methylaspartate
Wounds and Injuries
Spectrin
Dendrites
Calcium
Neurites
Proteolysis
Peptide Hydrolases
Western Blotting
Immunohistochemistry
In Vitro Techniques
Membranes
calpain inhibitors
Antibodies
Proteins

Keywords

  • calpain
  • cell culture
  • cytoskeleton
  • excitotoxicity
  • glutamate
  • neuronal injury
  • spectrin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Calpain activation contributes to dendritic remodeling after brief excitotoxic injury in vitro. / Faddis, Brian T.; Hasbani, M. Josh; Goldberg, Mark P.

In: Journal of Neuroscience, Vol. 17, No. 3, 1997, p. 951-959.

Research output: Contribution to journalArticle

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