26th Annual Meeting of the Society for Neuroscience, November 16-21, 1996, Washington, D.C.

Protein kinase C inhibitors attenuate the protective effect of class I metabotropic glutamate receptor agonists against hypoxic/hypoglycemic injury in hippocampal slices

J. Breder, U. H. Schröder, T. Jäger, T. Opitz, C. F. Sabelhaus, D. Balschun* and K. Reymann


During hypoxia and ischemia an excessive release of glutamate eventually leads to sustained neuronal damage. To investigate the influence of metabotropic glutamate receptors (mGluRs) on neuronal injury caused by cerebral hypoxia/ischemia, we employed an in vitro model of hypoxia/hypoglycemia.
Hippocampal slices from 7-week-old male Wistar rats were transiently exposed to an oxygen and glucose free environment in an interface chamber. The synaptically evoked population spike in the CA1 region was taken as a measure of neuronal viability.
Under control conditions the population spike amplitude recovered incompletely (48.5±3.6 % of baseline values) within one hour after termination of the hypoxic/hypoglycemic event. The specific class I mGluR agonists trans azetidine2,4 dicarboxylic acid (trans ADA, 100 mM) and 3,5 dihydroxy-phenylglycine (DHPG, 10 mM) were highly protective (89.3±3.8 % and 93.8 ±2.1% of baseline values respectively) when applied before the event. Co-application of the protein kinase C (PKC) inhibitors staurosporine (100 nM) and chelerythrine (30 mM) reduced the recovery rate to 39.3±7.9 % and 57.1±11.7% of baseline values respectively.
Our data suggest that the activation of the phospholipase C pathway prior to hypoxia/hypoglycemia exhibits a pronounced protective effect which depends on protein phosphorylation. They indicate that the protective effect of class I mGluR agonists is mediated by PKC which must be activated prior to the onset of the hypoxic/hypoglycemic event.
This work was supported by BMBF grant BEO 21-0319998B.

Back to My job
Feel free to send e-mail me! jaeger@ifn-magdeburg.de