Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

Jiménez-Mateos, Eva M. and Engel, Tobias and Merino-Serrais, Paula and McKiernan, Ross C. and Tanaka, Katsuhiro and Mouri, Genshin and Sano, Takanori and O’Tuathaigh, Colm and Waddington, John L. and Prenter, Suzanne and Delanty, Norman and Farrell, Michael A. and O’Brien, Donncha F. and Conroy, Ronán M. and Stallings, Raymond L. and Felipe Oroquieta, Javier de and Henshall, David C. (2012). Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects. "Nature", v. 18 (n. 7); pp. 1087-1094. ISSN 0028-0836. https://doi.org/10.1038/nm.2834.

Description

Title: Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects
Author/s:
  • Jiménez-Mateos, Eva M.
  • Engel, Tobias
  • Merino-Serrais, Paula
  • McKiernan, Ross C.
  • Tanaka, Katsuhiro
  • Mouri, Genshin
  • Sano, Takanori
  • O’Tuathaigh, Colm
  • Waddington, John L.
  • Prenter, Suzanne
  • Delanty, Norman
  • Farrell, Michael A.
  • O’Brien, Donncha F.
  • Conroy, Ronán M.
  • Stallings, Raymond L.
  • Felipe Oroquieta, Javier de
  • Henshall, David C.
Item Type: Article
Título de Revista/Publicación: Nature
Date: July 2012
ISSN: 0028-0836
Volume: 18
Subjects:
Faculty: Centro de Tecnología Biomédica (CTB) (UPM)
Department: Otro
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Abstract

Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation.

More information

Item ID: 19825
DC Identifier: http://oa.upm.es/19825/
OAI Identifier: oai:oa.upm.es:19825
DOI: 10.1038/nm.2834
Official URL: http://www.nature.com/nm/journal/v18/n7/full/nm.2834.html
Deposited by: Memoria Investigacion
Deposited on: 14 Oct 2013 17:40
Last Modified: 21 Apr 2016 21:24
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