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J Neurol Sci. 2012 Mar 15;314(1-2):104-10. doi: 10.1016/j.jns.2011.10.012. Epub 2011 Oct 28.

CaMKII antisense oligodeoxynucleotides protect against ischemia-induced neuronal death in the rat hippocampus.

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Key Laboratory of Biological Cancer Therapy of Jiangsu Province, Xuzhou 221002, China.


The present study was performed to investigate the effects of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) antisense oligodeoxynucleotides (ODNs) on the assembly of the CaMKII·GluR6·PSD-95 signaling module, GluR6 serine phosphorylation and c-Jun N-terminal kinase 3 (JNK3) activation. A further aim was to determine the neuroprotective mechanism of CaMKII antisense ODNs against ischemia-reperfusion (I/R)-induced neuronal death in the rat hippocampus. CaMKII antisense ODNs were intracerebroventricularly infused to inhibit CaMKII expression once daily for 3 days prior to the induction of ischemia. Transient cerebral ischemia (15 min) and reperfusion were induced by four-vessel occlusion in Sprague-Dawley rats as an animal model for transient cerebral I/R. The expression of related proteins was examined by immunoprecipitation and immunoblotting. Neuronal death in the rat hippocampus was detected by histology and histochemistry. The results indicate that CaMKII antisense ODNs inhibit several of the processes that are normally induced by cerebral I/R, including CaMKII expression, increased CaMKII·GluR6·PSD-95 signaling module assembly, GluR6 serine phosphorylation and JNK3 activation. Alternatively, CaMKII antisense ODNs also exhibit a significant neuroprotective role against cerebral I/R-induced cell death. These results provide the first evidence that CaMKII antisense ODNs can exert neuroprotective effects on cerebral I/R-induced cell death. The possible molecular mechanisms underlying this effect include 1) an inhibition of CaMKII expression and subsequent suppression of the assembly of the CaMKII·GluR6·PSD-95 signaling module, 2) GluR6 serine phosphorylation, and 3) reduced JNK3 activation.

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