School of Biomedical Sciences and Pharmacy, and The Hunter Medical Research Institute, Faculty of Health, The University of Newcastle, Callaghan, New South Wales, Australia.
J Cereb Blood Flow Metab. 2012 Dec;32(12):2181-92. doi: 10.1038/jcbfm.2012.124. Epub 2012 Aug 29.
Different brain regions exhibit differing sensitivities to ischemia/excitotoxicity. Whether these differences are due to perfusion or intrinsic factors has not been established. Herein, we found no apparent association between sensitivity to ischemia/excitotoxicity and the level of expression or basal phosphorylation of calcium/calmodulin-stimulated protein kinase II (αCaMKII) or glutamate receptors. However, we demonstrated significant differences in CaMKII-mediated responses after ischemia/excitotoxic stimulation in striatum and cortex. In vivo ischemia and in vitro excitotoxic stimulation produced more rapid phosphorylation of Thr253-αCaMKII in striatum compared with cortex, but equal rates of Thr286-αCaMKII phosphorylation. Phosphorylation by CaMKII of Ser831-GluA1 and Ser1303-GluN2B occurred more rapidly in striatum than in cortex after either stimulus. The differences between brain regions in CaMKII activation and its effects were not accounted for by differences in the expression of αCaMKII, glutamate receptors, or density of synapses. These results implicate intrinsic tissue differences in Thr253-αCaMKII phosphorylation in the differential sensitivities of brain regions to ischemia/excitotoxicity.
不同的脑区对缺血/兴奋毒性表现出不同的敏感性。这些差异是由于灌注还是内在因素造成的尚未确定。在此，我们发现缺血/兴奋毒性敏感性与钙/钙调蛋白刺激蛋白激酶 II（αCaMKII）或谷氨酸受体的表达或基础磷酸化水平之间没有明显的关联。然而，我们在纹状体和皮质的缺血/兴奋刺激后证明了 CaMKII 介导的反应存在显著差异。体内缺血和体外兴奋毒性刺激导致纹状体中 Thr253-αCaMKII 的磷酸化比皮质更快，但 Thr286-αCaMKII 的磷酸化速率相同。在两种刺激后，CaMKII 对 Ser831-GluA1 和 Ser1303-GluN2B 的磷酸化在纹状体比在皮质更快发生。脑区之间 CaMKII 激活及其作用的差异不能用 αCaMKII、谷氨酸受体或突触密度的差异来解释。这些结果表明，脑区对缺血/兴奋毒性敏感性的差异与 Thr253-αCaMKII 磷酸化的内在组织差异有关。
