Selective loss of neuronal Na+-dependent phosphate cotransporter mRNA in CA1 pyramidal neuron following global ischemia.
A recently identified neuronal Na+-dependent phosphate cotransporter (rBNPI) has been shown to import inorganic phosphate (P(i)) required for the production of high-energy phosphates which are vital to neuronal energy metabolism. In the present study, we have examined the expression of rBNPI mRNA in the hippocampus of rats subjected to 30 min of global ischemia by four-vessel occlusion. In situ hybridization reveals that transient forebrain ischemia results in a selective reduction in rBNPI mRNA expression in CA1 pyramidal neurons of the hippocampus. Expression of rBNPI is significantly reduced by 24 h and completely absent at 72 h following global ischemia when CA1 pyramidal neurons begin to show cell damage. By contrast, there is no change in the expression of Nedd2 mRNA, a developmentally regulated cell death gene, in CA1 pyramidal neurons at these same time points. The loss of rBNPI transcripts appears to be selective for CA1 pyramidal neurons since rBNPI mRNA expression is unchanged in neurons of the CA2-CA4 pyramidal cell layers following global ischemia. Our data indicate that an early reduction of rBNPI transcripts may contribute to a reduction in P(i)-dependent energy metabolism or signal transduction which has been reported in CA1 hippocampal neurons following global ischemia.
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Division of Neuroscience Research, Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana 46285, USA.
Stephenson
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Wu
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Smalstig
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Clemens
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Paul
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D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D003546:Cysteine Endopeptidases / Q000096:biosynthesis; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D016548:Prosencephalon / Q000503:physiopathology; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014158:Transcription, Genetic
D002352:Carrier Proteins; D015347:RNA Probes; D012333:RNA, Messenger; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; C490359:Casp2 protein, rat; D003546:Cysteine Endopeptidases