Morgan James, Alves Mariana, Conte Giorgia, Menéndez-Méndez Aida, de Diego-Garcia Laura, de Leo Gioacchino, Beamer Edward, Smith Jonathon, Nicke Annette, Engel Tobias
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland.
FutureNeuro, Science Foundation Ireland Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland.
Neurosci Bull. 2020 Nov;36(11):1242-1258. doi: 10.1007/s12264-020-00573-9. Epub 2020 Sep 7.
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.
越来越多的证据表明,ATP门控P2X7受体导致大脑兴奋性增加。虽然癫痫持续状态后及癫痫发作期间海马体和皮质中P2X7表达增加已得到反复证实,但P2X7的细胞类型特异性表达及其在海马体外脑结构中的表达仍未得到充分研究。在本研究中,通过使用过表达与荧光蛋白EGFP融合的P2X7的转基因小鼠模型来观察P2X7的表达。结果显示,杏仁核内注射 kainic 酸诱导癫痫持续状态后以及在包括海马体、皮质、纹状体、丘脑和小脑在内的不同脑区癫痫发作期间,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志物的共定位。这些数据表明,P2X7激活是不同脑结构中的一个共同病理标志,可能导致急性癫痫发作后及癫痫发作期间的脑部炎症和神经退行性变。