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Calpain and N-methyl-d-aspartate (NMDA)-induced excitotoxicity in rat retinas.
- Source :
-
Brain research [Brain Res] 2005 Jun 07; Vol. 1046 (1-2), pp. 207-15. - Publication Year :
- 2005
-
Abstract
- Calpain-mediated proteolysis has been implicated as a major process in neuronal cell death in both acute insults and the chronic neurodegenerative disorders in the central nerves system. However, activation of calpain also plays a protective function in the early phase of excitotoxic neuronal death. The exact role of calpains in neuronal death and recovery after exposure to N-methyl-D-aspartate (NMDA) is not clearly known. The purpose of present study was to examine the involvement of mu- and m-calpain in NMDA-induced excitotoxicity in the adult rat retina. Increased immunoreactivity of mu-calpain was noted in RGC layer cells and in the inner nuclear layer with maximal expression at 12 h after NMDA injection. This was further confirmed with Western blotting. TdT-mediated biotin-dUTP nick end labeling (TUNEL) positive cells in the inner retina co-localized with moderate or intense mu-calpain immunoreactivity. In contrast, there was no remarkable change in m-calpain immunoreactivity at any time point after NMDA injection. Simultaneous injection of 2 nmol of a calpain inhibitor (calpain inhibitor II) significantly reduced the number of TUNEL-positive cells in the inner retina at 18 h after NMDA injection and preserved RGC-like cells counted at 7 days after injection. The results of this study showed that mu-calpain may be involved in mediating NMDA-induced excitotoxicity in the rat retina and calpain inhibitors may play a therapeutic role in NMDA related disease.
- Subjects :
- Animals
Apoptosis drug effects
Blotting, Western
DNA Fragmentation drug effects
DNA Fragmentation physiology
Immunohistochemistry
In Situ Nick-End Labeling
Isoenzymes
Male
N-Methylaspartate
Neurons drug effects
Neurotoxins
Rats
Rats, Sprague-Dawley
Retina drug effects
Retina pathology
Retinal Diseases chemically induced
Apoptosis physiology
Calpain metabolism
Neurons enzymology
Retina enzymology
Retinal Diseases enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-8993
- Volume :
- 1046
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 15878434
- Full Text :
- https://doi.org/10.1016/j.brainres.2005.04.016