Wu X L, Ma D M, Zhang W, Zhou J S, Huo Y W, Lu M, Tang F R
Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an, Shaanxi 710061, China.
Department of Thoracic Surgery, The Ninth Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, China.
Epilepsy Res. 2018 Mar;141:64-72. doi: 10.1016/j.eplepsyres.2018.02.007. Epub 2018 Feb 17.
Gap junctions play an important role in the synchronization activity of coupled cells. Hippocampal inhibitory interneurons are involved in epileptogenesis and seizure activity, and express gap junction protein connexin (Cx) 36. Cx36 is also localized in the axons (mossy fibers) of granule cells in the dentate gyrus. While it has been documented that Cx36 is involved in epileptogenesis, there are still controversies regarding the expression levels of Cx36 at different developmental stages of human and animal models of epileptogenesis. In this study, the expression of Cx36 was investigated in the mouse hippocampus at 1 h, 4 h during pilocarpine-induced status epilepticus (PISE) and 1 week, 2 months after PISE. We found that Cx36 was down-regulated in neurons at different time points during and after PISE, whereas it was increased significantly in the stratum lucidum of CA3 area at 2 months after PISE. Double immunofluorescence indicated that Cx36 was localized in parvalbumin (PV) immunopositive interneuron in CA1 area and in mossy fibers and their terminals in the stratum lucidum of CA3 area. It suggests that decreased expression of Cx36 in interneurons may be related to less effective inhibitory control of excitatory activity of hippocampal principal neurons. However, the increased Cx36 immunopositive product in mossy fibers at the chronic stage after PISE may enhance the contacts between granule cells in the dentate gyrus and pyramidal neurons in CA3 area. The two different changes of Cx36 may be implicated in the epileptogenesis.
缝隙连接在耦合细胞的同步活动中起重要作用。海马抑制性中间神经元参与癫痫发生和癫痫发作活动，并表达缝隙连接蛋白连接蛋白（Cx）36。Cx36也定位于齿状回颗粒细胞的轴突（苔藓纤维）中。虽然已有文献记载Cx36参与癫痫发生，但关于Cx36在人类和动物癫痫发生模型不同发育阶段的表达水平仍存在争议。在本研究中，研究了匹罗卡品诱导的癫痫持续状态（PISE）期间1小时、4小时以及PISE后1周、2个月时小鼠海马中Cx36的表达。我们发现，在PISE期间及之后的不同时间点，神经元中的Cx36表达下调，而在PISE后2个月时，CA3区透明层中的Cx36表达显著增加。双重免疫荧光表明，Cx36定位于CA1区小白蛋白（PV）免疫阳性中间神经元以及CA3区透明层中的苔藓纤维及其终末。这表明中间神经元中Cx36表达降低可能与对海马主要神经元兴奋性活动的抑制控制效果减弱有关。然而，PISE后慢性期苔藓纤维中Cx36免疫阳性产物的增加可能增强齿状回颗粒细胞与CA3区锥体细胞之间的联系。Cx36的这两种不同变化可能与癫痫发生有关。
