Interleukin-10 prevents the hypoxia-induced decreases in expressions of AMPA receptor subunit GluA1 and alpha subunit of Ca(2+)/calmodulin-dependent protein kinase II in hippocampal neurons.

The goal of this study is to evaluate the effects of anti-inflammatory cytokine interleukin-10 (IL-10) on the repeated brief hypoxia-induced changes in expressions of AMPA receptor subunit GluA1 and α- and ß-subunit of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). The hypoxia-induced changes in the rat hippocampal slice CA1 neuronal activities were investigated by the method of field potentials recording. Subunit-specific antibodies staining of Western blots of hippocampal slice homogenates to characterize the receptor subunit GluA1 and α- and ß-subunit of CaMKII were used. IL-10 (1ng/ml) abolished the development of posthypoxic hyperexcitability in the CA1 pyramidal neurons induced by repeated brief hypoxia. This neuroprotective effect of IL-10 was rapidly developed within 10min after hypoxic episodes and accompanied by reversions of the hypoxia-induced decreases in expressions of AMPA receptor subunit GluA1 and α-subunit of CaMKII. These findings provide some evidence about existence of the novel mechanism underlying the rapid neuroprotective effect of anti-inflammatory cytokine IL-10 against hypoxia-induced neurological deteriorations.

The role of Ca2+/calmodulin-dependent protein kinase II in mechanisms underlying neuronal hyperexcitability induced by repeated, brief exposure to hypoxia or high K+ in rat hippocampal slices.

Analysis of extracellular recordings of evoked excitatory postsynaptic potentials and population spikes from rat hippocampal slices has previously revealed that repeated, brief exposures to high extracellular K(+) or to episodes of hypoxia induce a sustained (more than 3 h) hyperexcitability of CA1 pyramidal neurons accompanied with epileptiform activity which was dependent on activation of L-type Ca(2+) channels and N-methyl-D-aspartate receptors. Using in vitro phosphorylation assay we have found the significant increase of Ca(2+)-independent activity of Ca(2+)/calmodulin-dependent protein kinase II in CA1 region of hippocampal slices 60 min after the high extracellular K(+) and 60-80 min after the hypoxic episodes. These data suggest possible involvement of Ca(2+)/calmodulin-dependent protein kinase II in Ca(2+)-dependent mechanisms of the maintenance phase of the observed epileptiform activity.