Han Xin-Jia, Shi Zhong-Shan, Xia Luo-Xing, Zhu Li-Hui, Zeng Ling, Nie Jun-Hua, Xu Zao-Cheng, Ruan Yi-Wen
GHM Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, Guangdong 510632, China; Department of Anatomy, Jinan University School of Medicine, Guangzhou, Guangdong 510632, China.
GHM Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, Guangdong 510632, China.
Neuroscience. 2016 Jul 7;327:64-78. doi: 10.1016/j.neuroscience.2016.04.011. Epub 2016 Apr 16.
Excess glutamate release from the presynaptic membrane has been thought to be the major cause of ischemic neuronal death. Although both CA1 and CA3 pyramidal neurons receive presynaptic glutamate input, transient cerebral ischemia induces CA1 neurons to die while CA3 neurons remain relatively intact. This suggests that changes in the properties of pyramidal cells may be the main cause related to ischemic neuronal death. Our previous studies have shown that the densities of dendritic spines and asymmetric synapses in the CA1 area are increased at 12h and 24h after ischemia. In the present study, we investigated changes in synaptic structures in the CA3 area and compared the expression of glutamate receptors in the CA1 and CA3 hippocampal regions of rats after ischemia. Our results demonstrated that the NR2B/NR2A ratio became larger after ischemia although the expression of both the NR2B subunit (activation of apoptotic pathway) and NR2A subunit (activation of survival pathway) decreased in the CA1 area from 6h to 48h after reperfusion. Furthermore, expression of the GluR2 subunit (calcium impermeable) of the AMPA receptor class significantly decreased while the GluR1 subunit (calcium permeable) remained unchanged at the same examined reperfusion times, which subsequently caused an increase in the GluR1/GluR2 ratio. Despite these notable differences in subunit expression, there were no obvious changes in the density of synapses or expression of NMDAR and AMPAR subunits in the CA3 area after ischemia. These results suggest that delayed CA1 neuronal death may be related to the dramatic fluctuation in the synaptic structure and relative upregulation of NR2B and GluR1 subunits induced by transient global ischemia.
突触前膜谷氨酸释放过多一直被认为是缺血性神经元死亡的主要原因。尽管CA1和CA3锥体神经元都接受突触前谷氨酸输入，但短暂性脑缺血会导致CA1神经元死亡，而CA3神经元相对保持完整。这表明锥体细胞特性的改变可能是与缺血性神经元死亡相关的主要原因。我们之前的研究表明，缺血后12小时和24小时，CA1区树突棘和不对称突触的密度增加。在本研究中，我们调查了CA3区突触结构的变化，并比较了缺血后大鼠CA1和CA3海马区谷氨酸受体的表达。我们的结果表明，尽管再灌注后6小时至48小时CA1区NR2B亚基（凋亡途径激活）和NR2A亚基（存活途径激活）的表达均下降，但缺血后NR2B/NR2A比值变大。此外，在相同的再灌注时间点，AMPA受体类的GluR2亚基（钙不渗透）的表达显著下降，而GluR1亚基（钙渗透）保持不变，这随后导致GluR1/GluR2比值增加。尽管亚基表达存在这些显著差异，但缺血后CA3区突触密度或NMDAR和AMPAR亚基的表达没有明显变化。这些结果表明，延迟的CA1神经元死亡可能与短暂性全脑缺血诱导的突触结构剧烈波动以及NR2B和GluR1亚基的相对上调有关。
