Contributions of Adult-Generated Granule Cells to Hippocampal Pathology in Temporal Lobe Epilepsy: A Neuronal Bestiary.
Contributions of Adult-Generated Granule Cells to Hippocampal Pathology in Temporal Lobe Epilepsy: A Neuronal Bestiary.
复制标题
DOI：
10.3233/bpl-170056
复制
发表时间：
2018-08-10
期刊：
影响因子：
--
通讯作者：
Danzer SC
中科院分区：
文献类型：
--
作者：
Danzer SC
海马神经发生在哺乳动物（包括人类）的整个生命过程中持续存在。在颞叶癫痫的发展过程中，新产生的海马颗粒细胞异常整合到大脑中。异常包括新生细胞的异位定位、异常基底树突的从头形成和顶端树突树的破坏。颗粒细胞位置和树突结构的变化从根本上改变了这些细胞能够接受的输入类型，以及剩余输入的相对比例。树突异常还为海马体的反复兴奋创造了新的途径。这些异常被假设为有助于癫痫的发展，并且也可能是与疾病相关的认知障碍的基础。为了验证这一假设，研究人员在动物模型中使用了药理学和遗传学策略来改变神经发生率，或者彻底消除新生细胞。虽然研究结果喜忧参半，许多悬而未决的问题仍然存在，但许多研究现在表明，消融新生颗粒细胞可以改善癫痫的疾病。总之，研究结果为继续阐明新生颗粒细胞在癫痫中的作用提供了强有力的理论基础：既可以理解疾病的基本机制，也可以作为癫痫的潜在新疗法。
Hippocampal neurogenesis continues throughout life in mammals – including humans. During the development of temporal lobe epilepsy, newly-generated hippocampal granule cells integrate abnormally into the brain. Abnormalities include ectopic localization of newborn cells, de novo formation of abnormal basal dendrites, and disruptions of the apical dendritic tree. Changes in granule cell position and dendritic structure fundamentally alter the types of inputs these cells are able to receive, as well as the relative proportions of remaining inputs. Dendritic abnormalities also create new pathways for recurrent excitation in the hippocampus. These abnormalities are hypothesized to contribute to the development of epilepsy, and may underlie cognitive disorders associated with the disease as well. To test this hypothesis, investigators have used pharmacological and genetic strategies in animal models to alter neurogenesis rates, or ablate the newborn cells outright. While findings are mixed and many unanswered questions remain, numerous studies now demonstrate that ablating newborn granule cells can have disease modifying effects in epilepsy. Taken together, findings provide a strong rationale for continued work to elucidate the role of newborn granule cells in epilepsy: both to understand basic mechanisms underlying the disease, and as a potential novel therapy for epilepsy.