The ionotropic ATP-gated P2X7 receptor is an important contributor to inflammatory signaling cascades via the release of Interleukin-1β, as well as having roles in cell death, neuronal plasticity and the release of neurotransmitters. Accordingly, there is interest in targeting the P2X7 receptor for the treatment of epilepsy. However, the signaling pathways downstream of P2X7 receptor activation remain incompletely understood. Notably, recent studies showed that P2X7 receptor expression is controlled, in part, by microRNAs (miRNAs). Here, we explored P2X7 receptor-dependent microRNA expression by comparing microRNA expression profiles of wild-type (wt) and P2X7 receptor knockout mice before and after status epilepticus. Genome-wide microRNA profiling was performed using hippocampi from wt and P2X7 receptor knockout mice following status epilepticus induced by intra-amygdala kainic acid. This revealed that the genetic deletion of the P2X7 receptor results in distinct patterns of microRNA expression. Specifically, we found that in vehicle-injected control mice, the lack of the P2X7 receptor resulted in the up-regulation of 50 microRNAs and down-regulation of 35 microRNAs. Post-status epilepticus, P2X7 receptor deficiency led to the up-regulation of 44 microRNAs while 13 microRNAs were down-regulated. Moreover, there was only limited overlap among identified P2X7 receptor-dependent microRNAs between control conditions and post-status epilepticus, suggesting that the P2X7 receptor regulates the expression of different microRNAs during normal physiology and pathology. Bioinformatic analysis revealed that genes targeted by P2X7 receptor-dependent microRNAs were particularly overrepresented in pathways involved in intracellular signaling, inflammation, and cell death; processes that have been repeatedly associated with P2X7 receptor activation. Moreover, whereas genes involved in signaling pathways and inflammation were common among up- and down-regulated P2X7 receptor-dependent microRNAs during physiological and pathological conditions, genes associated with cell death seemed to be restricted to up-regulated microRNAs during both physiological conditions and post-status epilepticus. Taken together, our results demonstrate that the P2X7 receptor impacts on the expression profile of microRNAs in the brain, thereby possibly contributing to both the maintenance of normal cellular homeostasis and pathological processes.

离子型ATP门控的P2X7受体是炎症信号级联反应的重要贡献者 通过IL-1β的释放，以及在细胞死亡，神经元可塑性和神经递质的释放中起作用。因此，有兴趣靶向P2X7受体以治疗癫痫。但是，仍未完全了解P2X7受体激活下游的信号通路。值得注意的是，最近的研究表明P2X7受体的表达部分受microRNA（miRNA）的控制。在这里，我们通过比较癫痫持续状态前后野生型（wt）和P2X7受体敲除小鼠的microRNA表达谱，探索了P2X7受体依赖性的microRNA表达。在扁桃体内海藻酸引起的癫痫持续状态后，使用来自wt和P2X7受体敲除小鼠的海马体进行全基因组microRNA分析。这表明P2X7受体的基因缺失导致microRNA表达的不同模式。具体来说，我们发现在注射了媒介物的对照小鼠中，P2X7受体的缺乏导致50个microRNA的上调和35个microRNA的下调。状态癫痫后，P2X7受体的缺乏导致44个microRNA的上调，而13个microRNA的下调。此外，在对照条件和状态后癫痫发作之间鉴定的P2X7受体依赖性microRNA之间仅有有限的重叠，这表明P2X7受体在正常生理和病理过程中调节不同microRNA的表达。生物信息学分析表明，受P2X7受体依赖的microRNA靶向的基因在涉及细胞内信号传导，炎症和细胞死亡的途径中尤为突出。与P2X7受体激活反复相关的过程。此外，虽然在生理和病理状态下上调和下调的P2X7受体依赖性microRNA中普遍存在与信号通路和炎症相关的基因，但与细胞死亡相关的基因似乎仅限于在生理状态和生理后状态下上调的microRNA。 -癫痫持续状态。两者合计，我们的结果表明P2X7受体会影响大脑中microRNA的表达谱，