Type

Journal Article

Authors

David C Henshall
Javier deFelipe
Ross C McKiernan
Ronan M Conroy
Cristina R Reschke
James Reynolds
Natalia Rodriguez-Alvarez
Isabel Fernaud-Espinosa
Paula Merino-Serrais
Tobias Engel
and 1 others

Subjects

Biochemistry

Topics
spine pilocarpine status epilepticus microrna kainic acid dendritic spines morphometric analysis targeting

Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus. (2013)

Abstract Emerging data support roles for microRNA (miRNA) in the pathogenesis of various neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in dendrites of hippocampal neurons, where it negatively regulates spine volume. Recent work identified upregulation of miR-134 in experimental and human epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant effects against kainic acid-induced seizures and was associated with a reduction in dendritic spine number. In the present study, we measured dendritic spine volume in mice injected with miR-134-targeting antagomirs and tested effects of the antagomirs on status epilepticus triggered by the cholinergic agonist pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice given antagomirs compared to controls that received a scrambled sequence. Treatment of mice with miR-134 antagomirs did not alter performance in a behavioral test (novel object location). Status epilepticus induced by pilocarpine was associated with upregulation of miR-134 within the hippocampus of mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of animals that developed status epilepticus following pilocarpine and increased animal survival. In antagomir-treated mice that did develop status epilepticus, seizure onset was delayed and total seizure power was reduced. These studies provide in vivo evidence that miR-134 regulates spine volume in the hippocampus and validation of the seizure-suppressive effects of miR-134 antagomirs in a model with a different triggering mechanism, indicating broad conservation of anticonvulsant effects.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David C Henshall, Javier deFelipe, Ross C McKiernan, Ronan M Conroy, Cristina R Reschke, James Reynolds, Natalia Rodriguez-Alvarez, Isabel Fernaud-Espinosa, Paula Merino-Serrais, Tobias Engel and 1 others

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
RonĂ¡n Conroy
Royal College of Surgeons in Ireland
Total Publications: 150
 
3
Cristina R Reschke
Royal College of Surgeons in Ireland
Total Publications: 8
 
4
James P Reynolds
Royal College of Surgeons in Ireland
Total Publications: 8
 
5
Natalia Rodriguez-Alvarez
Royal College of Surgeons in Ireland
 
6
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66