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毛果芸香碱诱导癫痫持续状态后海马CA1区Map2的时空分布及小胶质细胞变化

Spatiotemporal profile of Map2 and microglial changes in the hippocampal CA1 region following pilocarpine-induced status epilepticus.

作者信息

Schartz Nicole D, Herr Seth A, Madsen Lauren, Butts Sarah J, Torres Ceidy, Mendez Loyda B, Brewster Amy L

机构信息

Department of Psychological Sciences, West Lafayette, IN 47907, USA.

School of Science and Technology, Universidad del Este, Carolina, PR 00984, Puerto Rico.

出版信息

Sci Rep. 2016 May 4;6:24988. doi: 10.1038/srep24988.

Abstract

Status epilepticus (SE) triggers pathological changes to hippocampal dendrites that may promote epileptogenesis. The microtubule associated protein 2 (Map2) helps stabilize microtubules of the dendritic cytoskeleton. Recently, we reported a substantial decline in Map2 that coincided with robust microglia accumulation in the CA1 hippocampal region after an episode of SE. A spatial correlation between Map2 loss and reactive microglia was also reported in human cortex from refractory epilepsy. New evidence supports that microglia modulate dendritic structures. Thus, to identify a potential association between SE-induced Map2 and microglial changes, a spatiotemporal profile of these events is necessary. We used immunohistochemistry to determine the distribution of Map2 and the microglia marker IBA1 in the hippocampus after pilocarpine-induced SE from 4 hrs to 35 days. We found a decline in Map2 immunoreactivity in the CA1 area that reached minimal levels at 14 days post-SE and partially increased thereafter. In contrast, maximal microglia accumulation occurred in the CA1 area at 14 days post-SE. Our data indicate that SE-induced Map2 and microglial changes parallel each other's spatiotemporal profiles. These findings may lay the foundation for future mechanistic studies to help identify potential roles for microglia in the dendritic pathology associated with SE and epilepsy.

摘要

癫痫持续状态(SE)会引发海马体树突的病理变化,这可能会促进癫痫的发生。微管相关蛋白2(Map2)有助于稳定树突细胞骨架的微管。最近,我们报告称,在一次SE发作后,Map2大幅下降,同时海马体CA1区出现大量小胶质细胞积聚。在难治性癫痫患者的大脑皮层中,也报告了Map2缺失与反应性小胶质细胞之间的空间相关性。新证据支持小胶质细胞可调节树突结构。因此,为了确定SE诱导的Map2与小胶质细胞变化之间的潜在关联,有必要了解这些事件的时空特征。我们采用免疫组织化学方法,确定了匹鲁卡品诱导SE后4小时至35天内海马体中Map2和小胶质细胞标志物IBA1的分布。我们发现,CA1区的Map2免疫反应性下降,在SE后14天降至最低水平,此后部分有所增加。相比之下,小胶质细胞在SE后14天在CA1区积聚达到最大值。我们的数据表明,SE诱导的Map2和小胶质细胞变化在时空特征上相互平行。这些发现可能为未来的机制研究奠定基础,以帮助确定小胶质细胞在与SE和癫痫相关的树突病理中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dffc/4855223/f6b7619c47b9/srep24988-f1.jpg

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