Type

Journal Article

Authors

Tobias Engel
David C Henshall
Miguel Diaz-Hernandez
Anindya Bhattacharya
Antonio R Artalejo
Michael Letavic
M Teresa Miras-Portugal
Detlev Boison
Guillaume Mesuret
Luiz Fernando Almeida Silva
and 12 others

Subjects

Biochemistry

Topics
hippocampus cytokine production status epilepticus microrna pro inflammatory high throughput brain injury targeting microrna targeting epileptogenic atp gated ionotropic p2x7 receptor epilepsy

microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus. (2015)

Abstract 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. P2X7R-gated 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.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed
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Ireland -> University College Dublin -> School of Computer Science

Full list of authors on original publication

Tobias Engel, David C Henshall, Miguel Diaz-Hernandez, Anindya Bhattacharya, Antonio R Artalejo, Michael Letavic, M Teresa Miras-Portugal, Detlev Boison, Guillaume Mesuret, Luiz Fernando Almeida Silva and 12 others

Experts in our system

1
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66
 
2
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
3
Miguel Diaz-Hernandez
Royal College of Surgeons in Ireland
Total Publications: 13
 
4
Anindya Bhattacharya
Royal College of Surgeons in Ireland
Total Publications: 4
 
5
Antonio R Artalejo
Royal College of Surgeons in Ireland
Total Publications: 4
 
6
M Teresa Miras-Portugal
Royal College of Surgeons in Ireland
Total Publications: 12