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Characterization of the Expression of the ATP-Gated P2X7 Receptor Following Status Epilepticus and during Epilepsy Using a P2X7-EGFP Reporter Mouse.
Neuroscience Bulletin ( IF 5.6 ) Pub Date : 2020-09-07 , DOI: 10.1007/s12264-020-00573-9
James Morgan 1 , Mariana Alves 1 , Giorgia Conte 1 , Aida Menéndez-Méndez 1 , Laura de Diego-Garcia 1 , Gioacchino de Leo 1 , Edward Beamer 1 , Jonathon Smith 1, 2 , Annette Nicke 3 , Tobias Engel 1, 2
Affiliation  

Mounting evidence suggests that the ATP-gated P2X7 receptor contributes to increased hyperexcitability in the brain. While increased expression of P2X7 in the hippocampus and cortex following status epilepticus and during epilepsy has been repeatedly demonstrated, the cell type-specific expression of P2X7 and its expression in extra-hippocampal brain structures remains incompletely explored. In this study, P2X7 expression was visualized by using a transgenic mouse model overexpressing P2X7 fused to the fluorescent protein EGFP. The results showed increased P2X7-EGFP expression after status epilepticus induced by intra-amygdala kainic acid and during epilepsy in different brain regions including the hippocampus, cortex, striatum, thalamus and cerebellum, and this was most evident in microglia and oligodendrocytes. Co-localization of P2X7-EGFP with cell type-specific markers was not detected in neurons or astrocytes. These data suggest that P2X7 activation is a common pathological hallmark across different brain structures, possibly contributing to brain inflammation and neurodegeneration following acute seizures and during epilepsy.



中文翻译:

使用 P2X7-EGFP 报告小鼠表征癫痫持续状态后和癫痫期间 ATP 门控 P2X7 受体的表达。

越来越多的证据表明,ATP 门控 P2X7 受体有助于增加大脑的过度兴奋。虽然在癫痫持续状态后和癫痫期间海马和皮质中 P2X7 的表达增加已被反复证明,但 P2X7 的细胞类型特异性表达及其在海马外脑结构中的表达仍未完全探索。在这项研究中,P2X7 表达通过使用与荧光蛋白 EGFP 融合的过表达 P2X7 的转基因小鼠模型进行可视化。结果显示,杏仁核内红藻氨酸诱导癫痫持续状态后和癫痫期间,海马、皮质、纹状体、丘脑和小脑等不同脑区的 P2X7-EGFP 表达增加,这在小胶质细胞和少突胶质细胞中最为明显。在神经元或星形胶质细胞中未检测到 P2X7-EGFP 与细胞类型特异性标记物的共定位。这些数据表明,P2X7 激活是不同大脑结构的常见病理标志,可能导致急性癫痫发作和癫痫期间的大脑炎症和神经变性。

更新日期:2020-09-08
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