@article{discovery10158025,
            note = {{\copyright} 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/).},
       publisher = {Society for Neuroscience},
           month = {October},
           pages = {1--9},
         journal = {eNeuro},
            year = {2022},
          volume = {9},
          number = {5},
           title = {Investigation of MicroRNA-134 as a Target against Seizures and SUDEP in a Mouse Model of Dravet Syndrome},
          author = {Gerbatin, RR and Augusto, J and Morris, G and Campbell, A and Worm, J and Langa, E and Reschke, CR and Henshall, DC},
             url = {https://doi.org/10.1523/ENEURO.0112-22.2022},
        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.},
        keywords = {Dravet syndrome; miR-134; oligonucleotides; seizure; SUDEP}
}