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

IM Araujo, Joana Gil, BP Carreira, Paul Mohapel, Åsa Petersén, PS Pinheiro, Denis Soulet, BA Bahr, Patrik Brundin, CM Carvalho

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)666-676
JournalJournal of Neurochemistry
Volume105
Issue number3
DOIs
Publication statusPublished - 2008

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Neuronal Survival (013212041), Translational Neuroendocrinology (013210010), Wallenberg Neuroscience Centre, Lund (0131000110)

Subject classification (UKÄ)

  • Neurosciences

Fingerprint

Dive into the research topics of 'Calpain activation is involved in early caspase-independent neurodegeneration in the hippocampus following status epilepticus'. Together they form a unique fingerprint.

Cite this