Experimental Epilepsy Research, Department of Neurosurgery, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Cereb Cortex. 2012 Jan;22(1):26-36. doi: 10.1093/cercor/bhr054. Epub 2011 May 13.
It is a matter of ongoing debate whether newly generated granule cells contribute to epileptic activity in the hippocampus. To address this question, we investigated neurogenesis and epileptiform activity (EA) along the hippocampal septotemporal axis in the intrahippocampal kainate (KA) mouse model for temporal lobe epilepsy. Multisite intrahippocampal in vivo recordings and immunolabeling for c-Fos showed that the KA-induced status epilepticus (SE) extended along the septotemporal axis of both hippocampi with stronger intensity at ipsilateral temporal and contralateral sites. Accordingly, we found a position-dependent increase in proliferation (incorporation of bromodeoxyuridine) and neurogenesis (immunolabeling for doublecortin): Both were selectively increased in the ipsilateral temporal and entire contralateral subgranular zone, sparing the septal region close to the injection site. The newborn neurons were hyperexcitable and functionally integrated into the hippocampal network as revealed by patch-clamp recordings. Analysis of chronic EA also showed a differential intensity pattern along the hippocampal axis: EA was low in the septal portion with prominent sclerosis and granule cell dispersion but most pronounced in the transition zone where neurogenesis reappeared. In conclusion, SE stimulates neurogenesis in a position-dependent manner and coincidence of neurogenesis and stronger EA distal to the injection site suggests a proepileptogenic effect of increased neurogenesis.
新生成的颗粒细胞是否有助于海马体中的癫痫活动，这是一个持续争论的问题。为了解决这个问题，我们研究了海人酸（KA）诱导颞叶癫痫模型中海马沿隔颞轴的神经发生和癫痫样活动（EA）。多部位海马内体内记录和 c-Fos 免疫标记显示，KA 诱导的癫痫持续状态（SE）沿着两个海马的隔颞轴延伸，同侧颞叶和对侧部位的强度更强。因此，我们发现增殖（溴脱氧尿苷掺入）和神经发生（双皮质素免疫标记）存在位置依赖性增加：同侧颞叶和整个对侧颗粒下区选择性增加，而靠近注射部位的隔区则不受影响。新生神经元兴奋性过高，并通过膜片钳记录显示其功能整合到海马网络中。对慢性 EA 的分析也显示了沿海马轴的不同强度模式：EA 在隔区部分较低，伴有明显的硬化和颗粒细胞弥散，但在神经发生再次出现的过渡区最为明显。总之，SE 以位置依赖的方式刺激神经发生，并且在注射部位远端神经发生和更强的 EA 同时出现，提示神经发生增加具有促癫痫发生的作用。
