Type

Journal Article

Authors

David C Henshall
Norman Delanty
Donncha F O'Brien
Michael A Farrell
Jørgen Kjems
Morten T Venø
Mairead Diviney
Catherine Mooney
Tobias Engel
Eva M Jimenez-Mateos
and 1 others

Subjects

Biology

Topics
status epilepticus sequencing video recordings supports rna epilepsy temporal lobe novel targets contribution

RNA sequencing of synaptic and cytoplasmic Upf1-bound transcripts supports contribution of nonsense-mediated decay to epileptogenesis. (2016)

Abstract The nonsense mediated decay (NMD) pathway is a critical surveillance mechanism for identifying aberrant mRNA transcripts. It is unknown, however, whether the NMD system is affected by seizures in vivo and whether changes confer beneficial or maladaptive responses that influence long-term outcomes such the network alterations that produce spontaneous recurrent seizures. Here we explored the responses of the NMD pathway to prolonged seizures (status epilepticus) and investigated the effects of NMD inhibition on epilepsy in mice. Status epilepticus led to increased protein levels of Up-frameshift suppressor 1 homolog (Upf1) within the mouse hippocampus. Upf1 protein levels were also higher in resected hippocampus from patients with intractable temporal lobe epilepsy. Immunoprecipitation of Upf1-bound RNA from the cytoplasmic and synaptosomal compartments followed by RNA sequencing identified unique populations of NMD-associated transcripts and altered levels after status epilepticus, including known substrates such as Arc as well as novel targets including Inhba and Npas4. Finally, long-term video-EEG recordings determined that pharmacologic interference in the NMD pathway after status epilepticus reduced the later occurrence of spontaneous seizures in mice. These findings suggest compartment-specific recruitment and differential loading of transcripts by NMD pathway components may contribute to the process of epileptogenesis.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David C Henshall, Norman Delanty, Donncha F O'Brien, Michael A Farrell, Jørgen Kjems, Morten T Venø, Mairead Diviney, Catherine Mooney, Tobias Engel, Eva M Jimenez-Mateos and 1 others

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Norman Delanty
Royal College of Surgeons in Ireland
Total Publications: 49
 
3
Donncha F O'Brien
Royal College of Surgeons in Ireland
Total Publications: 19
 
4
Michael A Farrell
Royal College of Surgeons in Ireland
Total Publications: 43
 
5
Mairead Diviney
Royal College of Surgeons in Ireland
Total Publications: 5
 
6
Catherine Mooney
University College Dublin
Total Publications: 63
 
7
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66
 
8
Eva M Jimenez-Mateos
Royal College of Surgeons in Ireland
Total Publications: 55