Liu Jian Xin, Cao Xia, Tang Yong Cheng, Liu Yong, Tang Feng Ru
Institute of Neurobiology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
J Neurochem. 2007 Feb;100(4):1072-88. doi: 10.1111/j.1471-4159.2006.04272.x. Epub 2007 Dec 20.
The present study showed CCR7, CCR8, CCR9 and CCR10 in the normal Swiss mouse hippocampus at both protein and mRNA levels. CCR7, CCR9 and CCR10 were mainly localized in hippocampal principal cells and some interneurons. CCR9 was also found in the mossy fibres and/or terminals, suggesting an axonal or presynaptic localization, and CCR10 in apical dendrites of pyramidal neurons in the CA1 area. CCR8 was observed in interneurons. Double-labelling immunocytochemistry revealed that most of calbindin (CB)-, calretinin (CR)- and parvalbumin (PV)-immunopositive neurons expressed CCR7-10, except CR-immunopositive cells in which only 10 to 12% expressed CCR8. During and after pilocarpine-induced status epilepticus, progressive changes of each of CCR7, CCR8, CCR9 and CCR10 proteins occurred in different patterns at various time points. Sensitive real-time PCR showed similar change patterns at mRNA level. At the chronic stage, i.e. at 2 months after pilocarpine-induced status epilepticus, significant reduction of CCR7-10 expression in CB-, CR- and PV-immunpositive interneurons may suggest the phenotype change of surviving interneurons. Double labelling of CCR7, CCR8 and CCR9 with glial fibrillary acidic protein (GFAP) at the chronic stage may suggest an induced expression in reactive astrocytes. The present study may, therefore, for the first time, provide evidence that CCR7-10 may be involved in normal hippocampal activity. The demonstration of the progressive changes of CCR7-10 during and after status epilepticus may open a new area to reveal the mechanism of neuronal loss after status epilepticus and of epileptogenesis.
本研究显示，正常瑞士小鼠海马体中存在CCR7、CCR8、CCR9和CCR10蛋白及mRNA。CCR7、CCR9和CCR10主要定位于海马体主细胞和一些中间神经元。CCR9也存在于苔藓纤维和/或终末，提示其定位于轴突或突触前，而CCR10存在于CA1区锥体细胞的顶端树突中。CCR8在中间神经元中被观察到。双标免疫细胞化学显示，大多数钙结合蛋白（CB）、钙视网膜蛋白（CR）和小白蛋白（PV）免疫阳性神经元表达CCR7 - 10，但CR免疫阳性细胞中只有10%至12%表达CCR8。在毛果芸香碱诱导的癫痫持续状态期间及之后，CCR7、CCR8、CCR9和CCR10蛋白在不同时间点呈现不同模式的渐进性变化。灵敏的实时PCR显示在mRNA水平有类似的变化模式。在慢性期，即毛果芸香碱诱导的癫痫持续状态后2个月，CB、CR和PV免疫阳性中间神经元中CCR7 - 10表达显著降低，这可能提示存活中间神经元的表型改变。慢性期CCR7、CCR8和CCR9与胶质纤维酸性蛋白（GFAP）的双标可能提示在反应性星形胶质细胞中有诱导表达。因此，本研究可能首次提供证据表明CCR7 - 10可能参与正常海马体活动。癫痫持续状态期间及之后CCR7 - 10的渐进性变化的证明可能为揭示癫痫持续状态后神经元丢失及癫痫发生机制开辟一个新领域。
