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Calpain activation is involved in early caspase-independent neurodegeneration in the hippocampus following status epilepticus

Araujo, IM; Gil, Joana LU ; Carreira, BP; Mohapel, Paul LU ; Petersén, Åsa LU ; Pinheiro, PS; Soulet, Denis LU ; Bahr, BA; Brundin, Patrik LU and Carvalho, CM (2008) In Journal of Neurochemistry 105(3). p.666-676
Abstract
Evidence for increased calpain activity has been described in the hippocampus of rodent models of temporal lobe epilepsy. However, it is not known whether calpains are involved in the cell death that accompanies seizures. In this work, we characterized calpain activation by examining the proteolysis of calpain substrates and in parallel we followed cell death in the hippocampus of epileptic rats. Male Wistar rats were injected with kainic acid (KA; 10 mg/kg) intraperitoneally and sacrificed 24h later, after development of grade 5 seizures. We observed a strong Fluoro-Jade labelling in the CA1 and CA3 areas of the hippocampus in the rats that received KA, as compared to saline-treated rats. Immunohistochemistry and Western blot analysis for... (More)
Evidence for increased calpain activity has been described in the hippocampus of rodent models of temporal lobe epilepsy. However, it is not known whether calpains are involved in the cell death that accompanies seizures. In this work, we characterized calpain activation by examining the proteolysis of calpain substrates and in parallel we followed cell death in the hippocampus of epileptic rats. Male Wistar rats were injected with kainic acid (KA; 10 mg/kg) intraperitoneally and sacrificed 24h later, after development of grade 5 seizures. We observed a strong Fluoro-Jade labelling in the CA1 and CA3 areas of the hippocampus in the rats that received KA, as compared to saline-treated rats. Immunohistochemistry and Western blot analysis for the calpain-derived breakdown products of spectrin (SBDP) showed evidence of increased calpain activity in the same regions of the hippocampus where cell death is observed. No evidence was found for caspase activation, in the same conditions. Treatment with the calpain inhibitor MDL 28170 significantly prevented the neurodegeneration observed in CA1. Taken together, our data suggest that early calpain activation, but not caspase activation, is involved in neurotoxicity in the hippocampus after status epilepticus. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neurochemistry
volume
105
issue
3
pages
666 - 676
publisher
Wiley-Blackwell
external identifiers
  • pmid:18088374
  • wos:000255139200009
  • scopus:42449116702
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2007.05181.x
language
English
LU publication?
yes
id
66b86737-7770-4ca0-b07c-225f21973aff (old id 1143341)
date added to LUP
2008-07-30 14:11:46
date last changed
2017-11-05 04:11:15
@article{66b86737-7770-4ca0-b07c-225f21973aff,
  abstract     = {Evidence for increased calpain activity has been described in the hippocampus of rodent models of temporal lobe epilepsy. However, it is not known whether calpains are involved in the cell death that accompanies seizures. In this work, we characterized calpain activation by examining the proteolysis of calpain substrates and in parallel we followed cell death in the hippocampus of epileptic rats. Male Wistar rats were injected with kainic acid (KA; 10 mg/kg) intraperitoneally and sacrificed 24h later, after development of grade 5 seizures. We observed a strong Fluoro-Jade labelling in the CA1 and CA3 areas of the hippocampus in the rats that received KA, as compared to saline-treated rats. Immunohistochemistry and Western blot analysis for the calpain-derived breakdown products of spectrin (SBDP) showed evidence of increased calpain activity in the same regions of the hippocampus where cell death is observed. No evidence was found for caspase activation, in the same conditions. Treatment with the calpain inhibitor MDL 28170 significantly prevented the neurodegeneration observed in CA1. Taken together, our data suggest that early calpain activation, but not caspase activation, is involved in neurotoxicity in the hippocampus after status epilepticus.},
  author       = {Araujo, IM and Gil, Joana and Carreira, BP and Mohapel, Paul and Petersén, Åsa and Pinheiro, PS and Soulet, Denis and Bahr, BA and Brundin, Patrik and Carvalho, CM},
  issn         = {1471-4159},
  language     = {eng},
  number       = {3},
  pages        = {666--676},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Calpain activation is involved in early caspase-independent neurodegeneration in the hippocampus following status epilepticus},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2007.05181.x},
  volume       = {105},
  year         = {2008},
}