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戊四氮诱导的癫痫发作导致幼年雄性 Wistar 大鼠海马和颞叶皮质中小胶质细胞和星形胶质细胞表型的短期变化。

Pentylenetetrazole-Induced Seizures Cause Short-Term Changes in the Phenotype of Microglial and Astroglial Cells in the Hippocampus and Temporal Cortex of Young Male Wistar Rats.

机构信息

Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg, Russia.

出版信息

J Neurosci Res. 2024 Sep;102(9):e25385. doi: 10.1002/jnr.25385.

DOI:10.1002/jnr.25385
PMID:39305083
Abstract

Astrocytes and microglia can adopt two distinct phenotypes in various pathological processes: neurotoxic A1/M1 and neuroprotective A2/M2. Recent evidence suggests that these cells play a significant role in epileptogenesis. The objective of this study was to characterize the phenotype of astrocytes and microglial cells in the hippocampus and temporal cortex of young male Wistar rats at 3 h, 1, 3, and 7 days after pentylenetetrazole-induced seizures. RT-qPCR was employed to examine the expression of glial genes (Gfap, Aif1, Slc1a1, Slc1a2, Slc1a3, Itpr2, Gdnf, Bdnf, Fgf2, Tgfb, Il1b, Tnf, Il1rn, Lcn2, S100a10, Nlrp3, Arg1). The most notable alterations in the expression of glial genes were observed on the first day following seizures in the temporal cortex. An increase in the expression of the Gfap, Slc1a2, Slc1a1, Il1b, Tnfa, Bdnf, and Fgf2 genes, and the A2 astrocyte condition marker S100a10, was observed. An increase in the expression of the Gfap and Slc1a2 genes was observed in the hippocampus on the first day after seizures. However, in contrast to the changes observed in the cortex, the changes in the hippocampus were opposite for the Il1rn, Bdnf, Tgfb, and Arg1 genes. Nevertheless, the alterations in GFAP and EAAT2 protein levels were not corroborated by Western blot analysis. Conversely, a more comprehensive immunohistochemical analysis confirmed an augmentation in the number of GFAP-positive cells in the hippocampus 1 day after seizures. Based on the presented evidence, we can conclude that a single convulsive seizure episode in 3-week-old rats results in transient astroglial activation and polarization to a neuroprotective phenotype (A2).

摘要

星形胶质细胞和小胶质细胞在各种病理过程中可以表现出两种截然不同的表型

神经毒性 A1/M1 和神经保护 A2/M2。最近的证据表明,这些细胞在癫痫发生中起重要作用。本研究的目的是描述年轻雄性 Wistar 大鼠戊四氮诱导癫痫发作后 3 小时、1 天、3 天和 7 天海马和颞叶皮质中星形胶质细胞和小胶质细胞的表型。采用 RT-qPCR 检测神经胶质基因(Gfap、Aif1、Slc1a1、Slc1a2、Slc1a3、Itpr2、Gdnf、Bdnf、Fgf2、Tgfb、Il1b、Tnf、Il1rn、Lcn2、S100a10、Nlrp3、Arg1)的表达。在颞叶皮质中,癫痫发作后第一天观察到神经胶质基因表达的最显著变化。观察到 Gfap、Slc1a2、Slc1a1、Il1b、Tnfa、Bdnf 和 Fgf2 基因表达增加,以及 A2 星形胶质细胞标志物 S100a10 表达增加。癫痫发作后第一天,海马中观察到 Gfap 和 Slc1a2 基因表达增加。然而,与皮质变化相反,海马中 Il1rn、Bdnf、Tgfb 和 Arg1 基因的变化相反。然而,Western blot 分析并未证实 GFAP 和 EAAT2 蛋白水平的变化。相反,更全面的免疫组织化学分析证实,癫痫发作后 1 天海马中 GFAP 阳性细胞数量增加。根据目前的证据,我们可以得出结论,3 周龄大鼠单次惊厥发作导致短暂的星形胶质细胞激活和向神经保护表型(A2)极化。

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