eprintid: 10158025
rev_number: 7
eprint_status: archive
userid: 699
dir: disk0/10/15/80/25
datestamp: 2022-10-26 13:59:24
lastmod: 2022-10-26 13:59:24
status_changed: 2022-10-26 13:59:24
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Gerbatin, RR
creators_name: Augusto, J
creators_name: Morris, G
creators_name: Campbell, A
creators_name: Worm, J
creators_name: Langa, E
creators_name: Reschke, CR
creators_name: Henshall, DC
title: Investigation of MicroRNA-134 as a Target against Seizures and SUDEP in a Mouse Model of Dravet Syndrome
ispublished: pub
divisions: C08
divisions: G02
divisions: B02
divisions: UCL
divisions: D09
keywords: Dravet syndrome; miR-134; oligonucleotides; seizure; SUDEP
note: © 2022 Gerbatin et al. This is an open-access article distributed under the terms of the Creative
Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/).
abstract: Dravet syndrome (DS) is a catastrophic form of pediatric epilepsy mainly caused by noninherited mutations in the SCN1A gene. DS patients suffer severe and life-threatening focal and generalized seizures which are often refractory to available anti-seizure medication. Antisense oligonucleotides (ASOs) based approaches may offer treatment opportunities in DS. MicroRNAs are short noncoding RNAs that play a key role in brain structure and function by post-transcriptionally regulating gene expression, including ion channels. Inhibiting miRNA-134 (miR-134) using an antimiR ASO (Ant-134) has been shown to reduce evoked seizures in juvenile and adult mice and reduce epilepsy development in models of focal epilepsy. The present study investigated the levels of miR-134 and whether Ant-134 could protect against hyperthermia-induced seizures, spontaneous seizures and mortality (SUDEP) in F1.Scn1a(1/)tm1kea mice. At P17, animals were intracerebroventricular in-jected with 0.1–1 nmol of Ant-134 and subject to a hyperthermia challenge at postnatal day (P)18. A second cohort of P21 F1.Scn1a(1/)tm1kea mice received Ant-134 and were followed by video and EEG monitoring until P28 to track the incidence of spontaneous seizures and SUDEP. Hippocampal and cortical levels of miR-134 were similar between wild-type (WT) and F1.Scn1a(1/)tm1kea mice. Moreover, Ant-134 had no effect on hyperthermia-induced seizures, spontaneous seizures and SUDEP incidence were unchanged in Ant-134-treated DS mice. These findings suggest that targeting miR-134 does not have therapeutic applications in DS.
date: 2022-10
date_type: published
publisher: Society for Neuroscience
official_url: https://doi.org/10.1523/ENEURO.0112-22.2022
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1982400
doi: 10.1523/ENEURO.0112-22.2022
lyricists_name: Morris, Gareth
lyricists_id: GMORR48
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: eNeuro
volume: 9
number: 5
pagerange: 1-9
citation:        Gerbatin, RR;    Augusto, J;    Morris, G;    Campbell, A;    Worm, J;    Langa, E;    Reschke, CR;           Gerbatin, RR;  Augusto, J;  Morris, G;  Campbell, A;  Worm, J;  Langa, E;  Reschke, CR;  Henshall, DC;   - view fewer <#>    (2022)    Investigation of MicroRNA-134 as a Target against Seizures and SUDEP in a Mouse Model of Dravet Syndrome.                   eNeuro , 9  (5)   pp. 1-9.    10.1523/ENEURO.0112-22.2022 <https://doi.org/10.1523/ENEURO.0112-22.2022>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10158025/1/ENEURO.0112-22.2022.full.pdf