Pilocarpine-Induced Status Epilepticus Increases the Sensitivity of P2X7 and P2Y1 Receptors to Nucleotides at Neural Progenitor Cells of the Juvenile Rodent Hippocampus
Pilocarpine-Induced Status Epilepticus Increases the Sensitivity of P2X7 and P2Y1 Receptors to Nucleotides at Neural Progenitor Cells of the Juvenile Rodent Hippocampus
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DOI：
10.1093/cercor/bhw178
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发表时间：
2016-06
期刊：
影响因子：
3.7
通讯作者：
Katalin Rozmer;Po Gao;M. Araújo;M. T. Khan;Juan Liu;W. Rong;Yong Tang;H. Franke;U. Krügel
中科院分区：
文献类型：
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作者：
Katalin Rozmer;Po Gao;M. Araújo;M. T. Khan;Juan Liu;W. Rong;Yong Tang;H. Franke;U. Krügel
膜片钳记录显示转基因巢蛋白报告小鼠海马脑切片齿状回亚颗粒区神经祖细胞（NPCs）上存在P2X7受体。这些受体的激活引起NPCs静息膜电位附近的内向电流，而P2Y1受体的激活引起P2X7受体电流反转电位附近的外向电流。通过生物物理/药理学方法鉴定了两种受体。在匹罗卡品诱导的癫痫持续状态小鼠的脑切片中，或在含有匹罗卡品的外部培养基中培养的脑切片，P2X7和P2Y1受体的敏感性无一例外地增加。共聚焦显微镜证实了巢蛋白阳性npc的P2X7和P2Y1受体免疫阳性定位。复发性癫痫发作约5天后引起的大鼠一次性癫痫持续状态。中枢P2X7受体的阻断增加了癫痫发作的次数和严重程度。假设P2Y1受体在癫痫持续状态后可能会增加atp诱导的npc增殖/异位迁移；P2X7受体介导的坏死/凋亡可能会抵消这些作用，否则会导致复发性癫痫发作的慢性表现。
Patch-clamp recordings indicated the presence of P2X7 receptors at neural progenitor cells (NPCs) in the subgranular zone of the dentate gyrus in hippocampal brain slices prepared from transgenic nestin reporter mice. The activation of these receptors caused inward current near the resting membrane potential of the NPCs, while P2Y1 receptor activation initiated outward current near the reversal potential of the P2X7 receptor current. Both receptors were identified by biophysical/pharmacological methods. When the brain slices were prepared from mice which underwent a pilocarpine-induced status epilepticus or when brain slices were incubated in pilocarpine-containing external medium, the sensitivity of P2X7 and P2Y1 receptors was invariably increased. Confocal microscopy confirmed the localization of P2X7 and P2Y1 receptor-immunopositivity at nestin-positive NPCs. A one-time status epilepticus in rats caused after a latency of about 5 days recurrent epileptic fits. The blockade of central P2X7 receptors increased the number of seizures and their severity. It is hypothesized that P2Y1 receptors after a status epilepticus may increase the ATP-induced proliferation/ectopic migration of NPCs; the P2X7 receptor-mediated necrosis/apoptosis might counteract these effects, which would otherwise lead to a chronic manifestation of recurrent epileptic fits.