Alterations in [3H]MK-801, [3H]muscimol, [3H]cyclic AMP, and [3H]rolipram binding in the gerbil hippocampus following repeated ischemic insults.
Using [3H]MK-801, [3H]muscimol, [3H]cyclic AMP, and [3H]rolipram, we performed quantitative in vitro autoradiography to determine sequential alterations in the binding of N-methyl-D-aspartate and GABAA receptors, particulate cyclic AMP-dependent protein kinase, and cyclic AMP-selective phosphodiesterase, respectively, in the gerbil hippocampus following repeated brief ischemic insults. Changes from 1 h to 28 days after three 2-min ischemic insults at 1-h intervals were compared with those after 2 and 6 min of ischemia. We observed no alterations in the binding of all the four ligands throughout the observation period following 2 min of ischemia which produced no histological neuronal damage except for transient reductions in [3H]cyclic AMP binding during the early reperfusion period. [3H]Cyclic AMP binding in the CA1 subfield decreased one day after 6 min of ischemia and four days after three 2-min ischemic insults, and 62-65% of the binding was lost after 28 days. [3H]Rolipram binding in the CA1 subfield decreased one day after 6 min of ischemia and the binding was reduced by 45-50% after four and 28 days. Following three 2-min ischemic insults, [3H]rolipram binding decreased in the CA1 at one day, and decreased by 25-33% after 28 days. Both [3H]MK-801 and [3H]muscimol binding was preserved during the early reperfusion period after 6 min of ischemia and three 2-min ischemic insults. Reductions in [3H]MK-801 binding in CA1 were observed four days after ischemic insults when CA1 neuronal destruction was seen. After one month, approximately 50% of [3H]MK-801 binding was lost in CA1 in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
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H
Kato
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Araki
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K
Murase
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Kogure
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006651:Histocytochemistry; D008297:Male; D009118:Muscimol / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011760:Pyrrolidinones / Q000378:metabolism*; D020889:Rolipram
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D009118:Muscimol; D016291:Dizocilpine Maleate; D000242:Cyclic AMP; D011494:Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D020889:Rolipram