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皮质星形胶质细胞在创伤后癫痫发展后的转录组改变。

Transcriptomic alterations in cortical astrocytes following the development of post-traumatic epilepsy.

机构信息

Department of Biomedical Sciences and Pathobiology, Faculty of Health Sciences, Virginia Tech, 970 Washington Street SW, Life Sciences I; Rm 249 (MC0910), Blacksburg, VA, 24061, USA.

School of Neuroscience, Virginia Tech, Blacksburg, VA, 24061, USA.

出版信息

Sci Rep. 2024 Apr 10;14(1):8367. doi: 10.1038/s41598-024-58904-z.

DOI:10.1038/s41598-024-58904-z
PMID:38600221
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11006850/
Abstract

Post-traumatic epilepsy (PTE) stands as one of the numerous debilitating consequences that follow traumatic brain injury (TBI). Despite its impact on many individuals, the current landscape offers only a limited array of reliable treatment options, and our understanding of the underlying mechanisms and susceptibility factors remains incomplete. Among the potential contributors to epileptogenesis, astrocytes, a type of glial cell, have garnered substantial attention as they are believed to promote hyperexcitability and the development of seizures in the brain following TBI. The current study evaluated the transcriptomic changes in cortical astrocytes derived from animals that developed seizures as a result of severe focal TBI. Using RNA-Seq and ingenuity pathway analysis (IPA), we unveil a distinct gene expression profile in astrocytes, including alterations in genes supporting inflammation, early response modifiers, and neuropeptide-amidating enzymes. The findings underscore the complex molecular dynamics in astrocytes during PTE development, offering insights into therapeutic targets and avenues for further exploration.

摘要

创伤性脑损伤(TBI)后癫痫(PTE)是其众多使人衰弱的后果之一。尽管它对许多人产生了影响,但目前的治疗方案选择有限,我们对潜在的发病机制和易感性因素的理解仍不完整。在癫痫发生的潜在因素中,星形胶质细胞作为一种神经胶质细胞,引起了广泛关注,因为它们被认为在 TBI 后会促进大脑过度兴奋和癫痫发作。本研究评估了源自因严重局灶性 TBI 而发生癫痫动物的皮质星形胶质细胞的转录组变化。通过 RNA-Seq 和 IPA 分析,我们揭示了星形胶质细胞中独特的基因表达谱,包括支持炎症、早期反应调节剂和神经肽酰胺酶的基因的改变。这些发现强调了 PTE 发展过程中星形胶质细胞的复杂分子动态,为治疗靶点和进一步探索提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8950/11006850/ef4446995f5c/41598_2024_58904_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8950/11006850/dbbd499c899c/41598_2024_58904_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8950/11006850/19fd95a1dff3/41598_2024_58904_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8950/11006850/f709b77adce7/41598_2024_58904_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8950/11006850/ef4446995f5c/41598_2024_58904_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8950/11006850/dbbd499c899c/41598_2024_58904_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8950/11006850/19fd95a1dff3/41598_2024_58904_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8950/11006850/f709b77adce7/41598_2024_58904_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8950/11006850/ef4446995f5c/41598_2024_58904_Fig4_HTML.jpg

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本文引用的文献

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Efferocytosis is restricted by axon guidance molecule EphA4 via ERK/Stat6/MERTK signaling following brain injury.脑损伤后,轴突导向分子 EphA4 通过 ERK/Stat6/MERTK 信号限制噬血细胞作用。
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Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy.
非典型神经发生、星形胶质细胞增生和过度的门区中间神经元丢失与创伤后癫痫的发生有关。
Cells. 2023 Apr 25;12(9):1248. doi: 10.3390/cells12091248.
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Brain-Derived Neurotrophic Factor Inhibits the Function of Cation-Chloride Cotransporter in a Mouse Model of Viral Infection-Induced Epilepsy.脑源性神经营养因子在病毒感染诱导的癫痫小鼠模型中抑制阳离子-氯离子共转运体的功能。
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Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With Traumatic Brain Injury.单细胞RNA测序揭示与创伤性脑损伤相关的细胞和转录变化。
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