Pilocarpine-induced status epilepticus increases cell proliferation in the dentate gyrus of adult rats via a 5-HT1A receptor-dependent mechanism
Pilocarpine-induced status epilepticus increases cell proliferation in the dentate gyrus of adult rats via a 5-HT1A receptor-dependent mechanism
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DOI：
10.1016/s0006-8993(02)03989-6
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发表时间：
2003-03-14
期刊：
影响因子：
2.9
通讯作者：
Jacobs, BL
中科院分区：
文献类型：
--
作者：
Radley, JJ;Jacobs, BL
齿状回在一生中不断产生颗粒神经元。苔藓纤维，颗粒神经元轴突，在临床和实验中均经历不典型发芽。苔藓纤维发芽（MFS）被假设为网络重组的基础，该网络重组被认为可能通过形成新的复发性兴奋回路而产生自发复发性癫痫发作。海马神经发生可能是MFS发展的关键步骤，因为它在匹罗卡品诱导的癫痫持续状态后至少增强了2倍。由于已知5-羟色胺（5-HT） 1A受体激活也会增加大鼠齿状回颗粒细胞的发生，反过来，该受体的阻断会减少它，我们研究了5-HT1A受体阻断是否会阻止癫痫诱导的神经发生增强。阻断癫痫诱导的神经发生的能力将为其在网络重组中的作用提供一个测试，特别是在MFS方面，这可能是癫痫发展的基础。在本研究中，我们发现在匹洛卡平治疗前后阻断5-HT1A受体可阻止癫痫发作诱导的海马细胞增殖和存活，并且通过5-HT1A受体拮抗剂（WAY-100,635）的慢性治疗来预防这种情况，并不能阻止MFS的发生或自发复发性癫痫发作。综上所述，这些结果表明5-HT1A受体的激活是激活癫痫诱导的齿状回细胞增殖和存活的关键步骤，但不是自发性复发性癫痫发作和MFS的发生。(C) 2002 Elsevier Science B.V.版权所有
The dentate gyrus continues to produce granule neurons throughout life. Mossy fibers, the axons of granule neurons, undergo atypical sprouting in both clinical and experimental mesial temporal lobe epilepsy. Mossy fiber sprouting (MFS) has been hypothesized to underlie the network reorganization that is thought to produce spontaneously recurring seizures, possibly via the formation of new recurrent excitatory circuits. Hippocampal neurogenesis may be a critical step in the development of MFS, given that it is enhanced by at least 2-fold in the aftermath of pilocarpine-induced status epilepticus. Since it is known that serotonin (5-HT) 1A receptor activation also increases granule cell genesis in the dentate gyrus in rats, and reciprocally, that blockade of this receptor decreases it, we examined whether 5-HT1A receptor blockade would prevent the seizure-induced enhancement of neurogenesis. The ability to block seizure-induced neurogenesis would provide a test for its role in the network reorganization, especially in regards to MFS, which might underlie seizure development. In the present study, it was found that blockade of the 5-HT1A receptor before and after pilocarpine treatment prevented seizure-induced hippocampal cell proliferation and survival, and, its prevention by chronic treatment with a 5-HT1A receptor antagonist (WAY-100,635) did not prevent the development of MFS or spontaneously recurring seizures. Taken together, these results suggest that 5-HT1A receptor activation is a critical step in the activation of seizure-induced cell proliferation and survival in the dentate gyrus, however, not for the onset of spontaneously recurrent seizures and MFS. (C) 2002 Elsevier Science B.V. All rights reserved.