Changes in subunit composition of AMPA type glutamate receptors in CA1 neurons of the gerbil hippocampus after transient cerebral ischemia.
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This study was undertaken to evaluate the possible changes in the subunit composition of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) type glutamate receptor (GluR) in the hippocampal CA1 neurons which are vulnerable to ischemic insult. Cerebral ischemia was produced transiently by occluding both carotid arteries of Mongolian gerbils for 5 min. In situ hybridization histochemistry with oligonucleotide probes for GluR1-4 mRNAs and immunocytochemistry for either GluR1, the combination of GluR2 and G1uR3 (GluR2/3), or GluR4 were performed at 1 and 3 days after ischemia. Sham-operated animals had high levels of expression of mRNAs encoding G1uR1-3 throughout the hippocampus, while they had low levels of expression of GluR4 in the CA1-3 neurons. After 1 day of recirculation, the levels of G1uR1 and GluR3 mRNAs decreased dramatically in the CA1 neurons, and was no longer detectable at 3 days after the ischemic insult. In contrast, GluR2 mRNA showed only a slight decrease at day 1, and had decreased even further at 3 days. The levels of G1uR4 mRNA, which were observed mainly in the interneurons, changed very little during the entire recirculation period. The immunocytochemical study revealed that GluR1 and GluR2/3 proteins were distributed evenly along the apical dendrites in sham-operated gerbils. By 1 day after the ischemic insult, these immunoreactivities were still observed, but appeared to be localized in certain areas such as the postsynaptic membranes. No detectable G1uR1 or GluR2/3 immunoreactivity was moted at 3 days after the ischemic injury, although GluR4 was observed in the cells like interneurons which were resistant to ischemic insult such as the interneurons. The present results indicated that GluR2 mRNA was expressed more stably than that of either GluR1 or GluR3 in the CA1 pyramidal neurons during the early reperfusion period after a transient ischemic insult. This specific downregulation of receptor subunits in the CA1 neuron Suggests that the subunit composition of the AMPA receptors may be altered by ischemia. Since the Ca<SUP>2+</SUP> permeability of the AMPA receptor is determined by its subunit composition and since the heteromeric receptors containing the GluR2 subunit are Ca<SUP>2+</SUP>-impermeable, the stable expression of GluR2 could protect the cells by decreasing Ca<SUP>2+</SUP> influx into the CA1 cells, although this meeds to be confirmed by immunocytochemistry using an anti-GluR2 specific antibody. Our deta also imply that the difference in the vulnerability to ischemia between the pyramidal neurons and the interneurons may be due to coexpression of the GluR4 subunit.
- 一般社団法人 日本脳卒中学会の論文
一般社団法人 日本脳卒中学会 | 論文
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