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戊四氮诱导幼鼠急性惊厥后谷氨酸受体亚基的 mRNA 和蛋白表达改变。

Alterations in mRNA and Protein Expression of Glutamate Receptor Subunits Following Pentylenetetrazole-induced Acute Seizures in Young Rats.

机构信息

Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, Saint Petersburg 194223, Russia.

出版信息

Neuroscience. 2021 Aug 1;468:1-15. doi: 10.1016/j.neuroscience.2021.05.035. Epub 2021 Jun 5.

Abstract

Acute seizures can severely affect brain function and development. However, the underlying pathophysiological mechanisms are still poorly understood. Disturbances of the glutamatergic system are considered one of the critical mechanisms of neurological abnormalities. In the present study, we analyzed changes in the expression of NMDA and AMPA receptor subunits in the different brain regions (dorsal hippocampus, amygdala, and the medial prefrontal, temporal, and entorhinal cortex) using a pentylenetetrazole (PTZ) model of seizures in 3-week-old rats. A distinctive feature of this model is that the administration of PTZ causes severe acute seizures, which are not followed by the development of spontaneous recurrent seizures later on. Subunit expression was analyzed using qRT-PCR and Western blotting during the first week after seizures. The most pronounced alterations of mRNA and protein levels were observed in the dorsal hippocampus. We found decreased expression of the GluA2 mRNA 7 days after seizures (PSE7), as well as reduced GluN2a protein levels on PSE7. Significant alterations in the expression of different receptor subunits in the mRNA but not protein levels were observed in the entorhinal cortex and amygdala. In contrast, in the medial prefrontal and temporal cortex, we found almost no changes in the expression of the studied genes. The identified changes deepen our understanding of post-seizure disturbances in the developing brain and confirm that although various brain structures are involved in seizures, the hippocampus is the most vulnerable.

摘要

急性癫痫发作可严重影响大脑功能和发育。然而,其潜在的病理生理机制仍知之甚少。谷氨酸能系统的紊乱被认为是神经异常的关键机制之一。在本研究中,我们使用戊四氮(PTZ)致痫 3 周龄大鼠模型,分析了不同脑区(背侧海马、杏仁核以及内侧前额叶、颞叶和内嗅皮质)中 NMDA 和 AMPA 受体亚基表达的变化。该模型的一个显著特点是,PTZ 的给药会导致严重的急性癫痫发作,但之后不会发展为自发性复发性癫痫。在癫痫发作后的第一周,我们通过 qRT-PCR 和 Western blot 分析了亚基的表达情况。在背侧海马中观察到 mRNA 和蛋白水平的改变最为明显。我们发现,癫痫发作后 7 天(PSE7)时 GluA2 mRNA 的表达减少,以及 PSE7 时 GluN2a 蛋白水平降低。在杏仁核和内嗅皮质中,我们观察到不同受体亚基的表达在 mRNA 水平上有显著改变,但在蛋白水平上没有改变。相比之下,在 medial prefrontal 和 temporal 皮质中,我们发现研究基因的表达几乎没有变化。所鉴定的变化加深了我们对发育中大脑癫痫发作后紊乱的理解,并证实尽管各种脑结构都参与了癫痫发作,但海马体是最脆弱的。

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