Graduate Program of Translational Medicine, Department of Medicine, Federal University of São Paulo, São Paulo-SP, Brazil.
Developmental Disorders Program, Center of Biological Sciences and Health, Mackenzie Presbyterian University, São Paulo-SP, Brazil.
Endocrinology. 2018 Aug 1;159(8):3090-3104. doi: 10.1210/en.2018-00146.
Status epilepticus (SE) is an abnormally prolonged seizure that results from either a failure of mechanisms that terminate seizures or from initiating mechanisms that inherently lead to prolonged seizures. Here we report that mice experiencing a 3 hours of SE caused by pilocarpine exhibit a rapid increase in expression of type 2 iodothyronine deiodinase gene (Dio2) and a decrease in the expression of type 3 iodothyronine deiodinase gene in hippocampus, amygdala and prefrontal cortex. Type 3 iodothyronine deiodinase in hippocampal sections was seen concentrated in the neuronal nuclei, typical of ischemic injury of the brain. An unbiased analysis of the hippocampal transcriptome of mice undergoing 3 hours of SE revealed a number of genes, including those involved with response to oxidative stress, cellular homeostasis, cell signaling, and mitochondrial structure. In contrast, in mice with targeted disruption of Dio2 in astrocytes (Astro D2KO mouse), the highly induced genes in the hippocampus were related to inflammation, apoptosis, and cell death. We propose that Dio2 induction caused by SE accelerates production of T3 in different areas of the central nervous system and modifies the hippocampal gene expression profile, affecting the balance between adaptive and maladaptive mechanisms.
癫痫持续状态（SE）是一种异常延长的癫痫发作，它可能是由于终止癫痫发作的机制失效，或者是由于内在引发延长癫痫发作的机制所致。在这里，我们报告说，经历毛果芸香碱引起的 3 小时 SE 的小鼠在海马体、杏仁核和前额叶皮质中表现出 2 型碘甲状腺原氨酸脱碘酶基因（Dio2）表达的快速增加和 3 型碘甲状腺原氨酸脱碘酶基因表达的降低。海马体切片中的 3 型碘甲状腺原氨酸脱碘酶集中在神经元核中，这是大脑缺血损伤的典型特征。对经历 3 小时 SE 的小鼠海马转录组进行的无偏分析揭示了许多基因，包括参与氧化应激反应、细胞内稳态、细胞信号转导和线粒体结构的基因。相比之下，在星形胶质细胞中靶向敲除 Dio2 的小鼠（Astro D2KO 小鼠）中，海马体中高度诱导的基因与炎症、细胞凋亡和细胞死亡有关。我们提出，SE 引起的 Dio2 诱导加速了 T3 在中枢神经系统不同区域的产生，并改变了海马体的基因表达谱，影响了适应性和失调性机制之间的平衡。
