AntimiR targeting of microRNA-134 reduces seizures in a mouse model of Angelman syndrome
Aoife Campbell, Gareth Morris, Albert Sanfeliu, Joana Augusto, Elena Langa, Jaideep Kesavan, Thanh Ngoc Nguyen, Ronán Conroy, Jesper Worm, Lukasz Jan Kielpinski, Mads A. Jensen, Meghan T. Miller, Thomas Kremer, Cristina R. Reschke, David C. Henshall
Abstract
). Nevertheless, intracerebroventricular injection of an antimiR oligonucleotide inhibitor of miR-134 (Ant-134) reduced audiogenic seizure severity over multiple trials in 21- and 42-day-old AS mice. Interestingly, Ant-134 also improved distance traveled and center crossings of AS mice in the open-field test. Finally, we show that silencing miR-134 can upregulate targets of miR-134 in neurons differentiated from Angelman patient-derived induced pluripotent stem cells. These findings indicate that silencing miR-134 and possibly other microRNAs could be useful to treat clinically relevant phenotypes with a later developmental window in AS.