RT Journal Article
T1 microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus
A1 Jimenez-Mateos, Eva M.
A1 Arribas Blázquez, Marina
A1 Sanz-Rodriguez, Amaya
A1 Concannon, Caoimhin
A1 Olivos Ore, Luis Alcides
A1 Reschke, Cristina R.
A1 Mooney, Claire M.
A1 Mooney, Catherine
A1 Lugara, Eleonora
A1 Morgan, James
A1 Langa, Elena
A1 Jimenez-Pacheco, Alba
A1 Silva, Luiz Fernando Almeida
A1 Mesuret, Guillaume
A1 Boison, Detlev
A1 Miras Portugal, María Teresa
A1 Letavic, Michael
A1 Rodríguez Artalejo, Antonio
A1 Bhattacharya, Anindya
A1 Díaz Hernández, Miguel
A1 Henshall, David C.
A1 Engel, Tobias
AB The ATP-gated ionotropic P2X7 receptor (P2X7R) modulates glial activation, cytokine production and neurotransmitter release following brain injury. Levels of the P2X7R are increased in experimental and human epilepsy but the mechanisms controlling P2X7R expression remain poorly understood. Here we investigated P2X7R responses after focal-onset status epilepticus in mice, comparing changes in the damaged, ipsilateral hippocampus to the spared, contralateral hippocampus. P2X7Rgated inward currents were suppressed in the contralateral hippocampus and P2rx7 mRNA was selectively uploaded into the RNA-induced silencing complex (RISC), suggesting microRNA targeting. Analysis of RISC-loaded microRNAs using a high-throughput platform, as well as functional assays, suggested the P2X7R is a target of microRNA-22. Inhibition of microRNA-22 increased P2X7R expression and cytokine levels in the contralateral hippocampus after status epilepticus and resulted in more frequent spontaneous seizures in mice. The major pro-inflammatory and hyperexcitability effects of microRNA-22 silencing were prevented in P2rx7-/- mice or by treatment with a specific P2X7R antagonist. Finally, in vivo injection of microRNA-22 mimics transiently suppressed spontaneous seizures in mice. The present study supports a role for post-transcriptional regulation of the P2X7R and suggests therapeutic targeting of microRNA-22 may prevent inflammation and development of a secondary epileptogenic focus in the brain.
PB Nature
SN 2045-2322
YR 2015
FD 2015
LK https://hdl.handle.net/20.500.14352/96699
UL https://hdl.handle.net/20.500.14352/96699
LA eng
NO Jimenez-Mateos EM, Arribas-Blazquez M, Sanz-Rodriguez A, Concannon C, Olivos-Ore LA, Reschke CR, Mooney CM, Mooney C, Lugara E, Morgan J, Langa E, Jimenez-Pacheco A, Silva LF, Mesuret G, Boison D, Miras-Portugal MT, Letavic M, Artalejo AR, Bhattacharya A, Diaz-Hernandez M, Henshall DC, Engel T. microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus. Sci Rep. 2015 Dec 3;5:17486. doi: 10.1038/srep17486. PMID: 26631939; PMCID: PMC4668358.
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Comunidad de Madrid
NO Health Research Board
NO Science Foundation Ireland
NO European Commission
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 18 dic 2025