Contribution of NMDA and Non-NMDA Receptors to In vivo Glutamate-Induced Calpain Activation in the Rat Striatum. Relation to Neuronal Damage
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Glutamate, the major excitatory neurotransmitter, can cause the death of neurons by a mechanism known as excitotoxicity. This is a calcium-dependent process and activation of the NMDA receptor subtype contributes mainly to neuronal damage, due to its high permeability to calcium. Activation of calpain, a calcium-dependent cysteine protease, has been implicated in necrotic excitotoxic neuronal death. We have investigated the contribution of NMDA and non-NMDA ionotropic receptors to calpain activation and neuronal death induced by the acute administration of glutamate into the rat striatum. Calpain activity was assessed by the cleavage of the cytoskeletal protein, α-spectrin. Caspase-3 activity was also studied because glutamate can also lead to apoptosis. Results show no caspase-3 activity, but a strong calpain activation involving both NMDA and non-NMDA receptors. Although neuronal damage is mediated mainly by the NMDA receptor subtype, it can not be attributed solely to calpain activity.
KeywordsNMDA AMPA Kainate Caspase-3 Calpain Neurotoxicity
This work was supported by IN213507 PAPPIT (UNAM) grant to LM and 167146 CONACYT and DGEP fellowships to P. Del Río supported this work.
- 14.Goll D, Thompson V, Li H et al (2002) The calpain system. Physiol Rev 83:731–801Google Scholar
- 29.Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, SidneyGoogle Scholar
- 38.Montiel T, Camacho A, Estrada-Sanchez AM et al (2005) Differential effects of the substrate inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (PDC) and the non-substrate inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA) of glutamate transporters on neuronal damage and extracellular amino acid levels in rat brain in vivo. Neuroscience 133:667–678PubMedCrossRefGoogle Scholar