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