Glutamate receptor changes associated with transient anoxia/hypoglycaemia in hippocampal slice cultures

Article Article scientifique Article Glutamate receptor changes associated with transient anoxia/hypoglycaemia in hippocampal slice cultures eng 2006 author Quintana Patrice 530308 author Alberi Stefano 28683 author Hakkoum David 559219 author Muller Dominique 26488 975-983 10.1111/j.1460-9568.2006.04617.x 16519662 0953-816X Transient anoxia/hypoglycaemia in organotypic hippocampal slice cultures, a model of transient brain ischaemia, ultimately results in delayed cell death. Although the mechanisms underlying this delayed death remain unknown, an increase in excitatory drive has been postulated. We report here that transient anoxia/hypoglycaemia in rat hippocampal slice cultures resulted in a 70-80% enhancement of evoked, alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) receptor-mediated, excitatory responses lasting over 60 min. This effect was prevented by blockade of N-methyl-d-aspartate (NMDA) receptors, did not involve changes of paired-pulse facilitation ratio, but was associated with a 50% increase in amplitude, but not frequency, of spontaneous miniature excitatory postsynaptic currents (mEPSCs). Consistent with this, paired recordings revealed the appearance of AMPA receptor-mediated EPSCs at previously silent synapses and occlusion by prior induction of long-term potentiation (LTP). Transient anoxia/hypoglycaemia further resulted in a 63% potentiation of evoked NMDA receptor-dependent synaptic responses, accounting for the 20% increase in ratio of AMPA to NMDA responses. No change in rectification properties of AMPA receptor-mediated currents could be detected within the first hour following anoxia/hypoglycaemia-induced potentiation. Western blot analyses of slice cultures exposed to either control conditions or a short anoxia/hypoglycaemia revealed a marked, 50-70% increase of GluR1, GluR2/3 and NR1 subunits 1 h, but not 15 min, after the anoxic/hypoglycaemic episode. This increase was blocked by an inhibitor of protein synthesis. Together these results indicate that a transient anoxia/hypoglycaemia is associated with a marked enhancement of excitatory transmission sharing similarities with the mechanisms underlying LTP, and is correlated with an increased synthesis of excitatory receptor subunits. Animals Animals, Newborn Anoxia/ metabolism/ pathology Blotting, Western/methods Dose-Response Relationship, Radiation Electric Stimulation/methods Excitatory Amino Acid Agonists/pharmacology Excitatory Postsynaptic Potentials/drug effects/physiology/radiation effects Gene Expression Regulation Hippocampus/ metabolism Hypoglycemia/ metabolism/ pathology N-Methylaspartate/pharmacology Patch-Clamp Techniques/methods Rats Receptors, Glutamate/ metabolism Time Factors Alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology Dewey 616.8 53 Département de neurosciences fondamentales 21A false European journal of neuroscience 23 4 c9565924-f30c-443f-8a61-fdc74e6a1d24 Article Restricted file1.pdf 5221272 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Glutamate receptor changes associated with transient anoxia/hypoglycaemia in hippocampal slice cultures	European journal of neuroscience			2006	639	0

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Quintana, Patrice