Disruption of the neurogenic potential of the dentate gyrus in a mouse model of temporal lobe epilepsy with focal seizures
Disruption of the neurogenic potential of the dentate gyrus in a mouse model of temporal lobe epilepsy with focal seizures
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DOI：
10.1111/j.1460-9568.2005.04386.x
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发表时间：
2005-10-01
影响因子：
3.4
通讯作者：
Fritschy, JM
中科院分区：
文献类型：
--
作者：
Kralic, JE;Ledergerber, DA;Fritschy, JM
成人海马神经发生在包括癫痫发作在内的多种刺激下增强。然而，神经发生和颞叶癫痫（TLE）的发展之间的关系仍然不清楚。在成年小鼠中单侧海马内注射红藻氨酸模拟了在人TLE中观察到的形态学特征（例如神经元损失、神经胶质增生、颗粒细胞分散和肥大）和慢性自发复发性部分性癫痫发作的发生。我们研究了红藻氨酸诱导的致痫灶对海马神经发生的影响，比较了癫痫持续状态和自发性复发性部分性癫痫发作后神经干细胞的增殖。红藻氨酸治疗后，颗粒下区的细胞增殖短暂增加。结果，对侧齿状回的神经发生受到刺激。与此相反，癫痫海马表现出强烈的神经原性电位降低，即使在自发性复发性部分性癫痫发作后，可能是由于改变了颗粒下区的神经原性生态位。这些结果表明，神经发生并不有助于癫痫灶的形成，并可能受到影响时，分散的齿状回颗粒细胞发生。因此，在TLE患者中，海马硬化和颗粒细胞分散可能在破坏海马神经发生的潜力中发挥重要作用。
Adult hippocampal neurogenesis is enhanced in response to multiple stimuli including seizures. However, the relationship between neurogenesis and the development of temporal lobe epilepsy (TLE) remains unclear. Unilateral intrahippocampal injection of kainate in adult mice models the morphological characteristics (e.g. neuronal loss, gliosis, granule cell dispersion and hypertrophy) and occurrence of chronic, spontaneous recurrent partial seizures observed in human TLE. We investigated the influence of a kainate-induced epileptogenic focus on hippocampal neurogenesis, comparing neural stem cell proliferation following status epilepticus and spontaneous recurrent partial seizures. Cell proliferation in the subgranular zone was transiently increased bilaterally after kainate treatment. As a result, neurogenesis was stimulated in the contralateral dentate gyrus. In contrast, the epileptic hippocampus exhibited a strongly reduced neurogenic potential, even after onset of spontaneous recurrent partial seizures, possibly due to an alteration of the neurogenic niche in the subgranular zone. These results show that neurogenesis does not contribute to the formation of the epileptic focus and may be affected when dispersion of dentate gyrus granule cells occurs. Therefore, in patients with TLE, hippocampal sclerosis and granule cell dispersion may play a significant role in disrupting the potential for hippocampal neurogenesis.