Caspase-3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation

Glia. 2007 Jul;55(9):954-65. doi: 10.1002/glia.20518.


Caspase-3 has classically been defined as the main executioner of programmed cell death. However, recent data supports the participation of this protease in non-apoptotic cellular events including cell proliferation, cell cycle regulation, and cellular differentiation. In this study, astroglial cleavage of caspase-3 was analyzed following excitotoxic damage in postnatal rats to determine if its presence is associated with apoptotic cell death, cell proliferation, or cytoskeletal remodeling. A well-characterized in vivo model of excitotoxicity was studied, where damage was induced by intracortical injection of N-methyl-D-asparate (NMDA) in postnatal day 9 rats. Our results demonstrate that cleaved caspase-3 was mainly observed in the nucleus of activated astrocytes in the lesioned hemisphere as early as 4 h postlesion and persisted until the glial scar was formed at 7-14 days, and it was not associated with TUNEL labeling. Caspase-3 enzymatic activity was detected at 10 h and 1 day postlesion in astrocytes, and co-localized with caspase-cleaved fragments of glial fibrillary acidic protein (CCP-GFAP). However, at longer survival times, when astroglial hypertrophy was observed, astroglial caspase-3 did not generally correlate with GFAP cleavage, but instead was associated with de novo expression of vimentin. Moreover, astroglial caspase-3 cleavage was not associated with BrdU incorporation. These results provide further evidence for a nontraditional role of caspases in cellular function that is independent of cell death and suggest that caspase activation is important for astroglial cytoskeleton remodeling following cellular injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects
  • Astrocytes / enzymology*
  • Astrocytes / pathology
  • Brain / enzymology*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Damage, Chronic / enzymology*
  • Brain Damage, Chronic / physiopathology
  • Caspase 3 / metabolism*
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Proliferation / drug effects
  • Cell Size / drug effects
  • Cytoskeleton / drug effects
  • Cytoskeleton / enzymology*
  • Cytoskeleton / pathology
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / chemically induced*
  • Gliosis / enzymology
  • Gliosis / physiopathology
  • Intermediate Filaments / drug effects
  • Intermediate Filaments / metabolism
  • Intermediate Filaments / pathology
  • Male
  • N-Methylaspartate / metabolism
  • N-Methylaspartate / toxicity
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / enzymology
  • Nerve Degeneration / physiopathology
  • Neurotoxins / metabolism
  • Neurotoxins / toxicity
  • Rats
  • Rats, Long-Evans
  • Vimentin / metabolism


  • Glial Fibrillary Acidic Protein
  • Neurotoxins
  • Vimentin
  • N-Methylaspartate
  • Caspase 3