Korean J Anat.  2003 Feb;36(1):77-88.

AMPA Receptor-Induced Neuronal Cell Death in Rat Hippocampus Following Transient Global Ischemia: Relationship to Calpain and Caspase-3 Expression

Affiliations
  • 1Department of Anatomy, School of Medicine, Dongguk University, Kyungju, Korea. jungyw2442@yahoo.co.kr
  • 2Department of Physiology, School of Medicine, Dongguk University, Kyungju, Korea.

Abstract

A central challenge in ischemia-induced neuronal death research is understanding the mechanisms by which apoptotic or necrotic cascades are initiated and affected. We tested potential roles for AMPA and NMDA receptor protein levels and activation of calpain, caspase-3 in the hippocampus at times after transient global ischemia when detectable necrotic or apoptotic cell damage was observed by neurofilament 200 (NF200) degradation, TUNEL, and H & E. We determined that the decrease in the AMPA receptor subunit, GluR2, in response to the transient global ischemia plays a major role in triggering the neuronal cell death in hippocampus. We also examined potential roles for calpain and caspase-3 in ischemic cell death and found that (1) calpain is activated at a time following caspase-3 activation and paralleled degradation of NR2A, NR2B, and GluR2 and irreversible necrotic neuronal changes, (2) caspase-3 is has their maximal expression at the time of highest apoptosis, (3) the NF200 degradation, one of the neuronal deathinducing factors was correlated well with the calpain activation and necrotic changes in the hippocampal CA1 neurons. These results suggest that the significant degradation of GluR2 subunits of AMPA receptor and calpain activation are possibly involved in NF 200 degradation-mediated necrotic hippocampal cell death after transient global ischemia.

Keyword

GluR2; Calpain; Caspase-3; Neurofilament 200

MeSH Terms

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid*
Animals
Apoptosis
Calpain*
Caspase 3*
Cell Death*
Hippocampus*
In Situ Nick-End Labeling
Ischemia*
N-Methylaspartate
Neurons*
Rats*
Receptors, AMPA
Calpain
Caspase 3
N-Methylaspartate
Receptors, AMPA
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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