Type

Journal Article

Authors

Tobias Engel
David C Henshall
Miguel Diaz-Hernandez
María Teresa Miras-Portugal
Donncha F O'Brien
Michael A Farrell
Norman Delanty
Rosa Gomez-Villafuertes
Mariana Alves

Subjects

Biochemistry

Topics
epilepsy temporal lobe cell death experimental models status epilepticus extracellular space kainic acid protein expression purinergic receptor

Expression and function of the metabotropic purinergic P2Y receptor family in experimental seizure models and patients with drug-refractory epilepsy. (2017)

Abstract ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy. Status epilepticus was induced using either intra-amygdala kainic acid or pilocarpine to characterize the acute- and long-term changes in hippocampal P2Y expression. P2Y expression was also investigated in brain tissue from patients with temporal lobe epilepsy. Finally, we analyzed the effects of two specific P2Y agonists, ADP and UTP, on seizure severity and seizure-induced cell death. Both intra-amygdala kainic acid and pilocarpine-induced status epilepticus increased the transcription of the uracil-sensitive P2Y receptors P2ry2 , P2ry4 , and P2ry6 and decreased the transcription of the adenine-sensitive P2Y receptors P2ry1 , P2ry12 , P2ry13 . Protein levels of P2Y1 , P2Y2 , P2Y4 , and P2Y6 were increased after status epilepticus, whereas P2Y12 expression was decreased. In the chronic phase, P2ry1 , P2ry2 , and P2ry6 transcription and P2Y1 , P2Y2 , and P2Y12 protein levels were increased with no changes for the other P2Y receptors. In hippocampal samples from patients with temporal lobe epilepsy, P2Y1 and P2Y2 protein expression was increased, whereas P2Y13 levels were lower. Demonstrating a functional contribution of P2Y receptors to seizures, central injection of ADP exacerbated seizure severity, whereas treatment with UTP decreased seizure severity during status epilepticus in mice. The present study is the first to establish the specific hippocampal expression profile and function of the P2Y receptor family after experimental status epilepticus and in human temporal lobe epilepsy and offers potential new targets for seizure control and disease modification.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Tobias Engel, David C Henshall, Miguel Diaz-Hernandez, María Teresa Miras-Portugal, Donncha F O'Brien, Michael A Farrell, Norman Delanty, Rosa Gomez-Villafuertes, Mariana Alves

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
M Teresa Miras-Portugal
Royal College of Surgeons in Ireland
Total Publications: 12
 
5
Donncha F O'Brien
Royal College of Surgeons in Ireland
Total Publications: 19
 
6
Michael A Farrell
Royal College of Surgeons in Ireland
Total Publications: 43
 
7
Norman Delanty
Royal College of Surgeons in Ireland
Total Publications: 49
 
8
Mariana Alves
Royal College of Surgeons in Ireland
Total Publications: 9