Conte, GiorgiaNguyen, Ngoc T.Alves, MarianaDe Diego García, LauraKenny, AidanNicke, AnnetteHenshall, David C.Jimenez-Mateos, Eva M.Engel, Tobias2026-02-182026-02-182020-08-12Conte G, Nguyen NT, Alves M, de Diego-Garcia L, Kenny A, Nicke A, Henshall DC, Jimenez-Mateos EM and Engel T (2020) P2X7 Receptor-Dependent microRNA Expression Profile in the Brain Following Status Epilepticus in Mice. Front. Mol. Neurosci. 13:127. doi: 10.3389/fnmol.2020.00127doi: 10.3389/fnmol.2020.00127https://hdl.handle.net/20.500.14352/132591Received: 21 April 2020; Accepted: 26 June 2020; Published: 12 August 2020. This work was supported by funding from the Health Research Board HRA-POR-2015-1243, Science Foundation Ireland (13/SIRG/2114, CDA17/CDA/4708 and co-funded under the European Regional Development Fund and by FutureNeuro industry partners 16/RC/3948), H2020 Marie Skłowdowksa-Curie Actions Individual Fellowship (753527), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (No. 766124), the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 602130 (EpimiRNA) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID: 335447717-SFB 1328. Data Availability Statement The original contributions presented in the study are publicly available. This data can be found in the Gene Expression Omnibus: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE153204, accession number GSE153204.The ionotropic ATP-gated P2X7 receptor is an important contributor to inflammatory signaling cascades via the release of Interleukin-1b, 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.engjournal article1662-5099https://doi.org/10.3389/fnmol.2020.00127open access616.853611.813.14Purinergic signalingP2X7 receptorstatus epilepticushippocampusmicroRNABiología molecular (Biología)Neurociencias (Biológicas)Bioquímica (Medicina)2403 Bioquímica2302.21 Biología Molecular2490 Neurociencias