ИСТИНА

# Contributed equally to this work 1 Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam 2 Ikerbasque, Achucarro Besque Center for Neuroscience and University of Basque Country Background: Under normal conditions, most hippocampal Neural Stem Cells (NSCs) give rise to neurons, and only a small percentage forms astrocytes. After kainic acid (KA)-induced status epilepticus (KA-SE) however, a strong shift in cell fate takes place, and many reactive NSCs generate astrocytes. The strong KA-induced activation results in a premature depletion of the NSC pool, which may contribute to epileptogenesis (Sierra 2015). Previously, our team has shown that miR-124 and miR-137 are upregulated in the Dentate Gyrus 3 days after SE. Consistently with this first observation, additional intrahippocampal administration of miR-124 and -137 aggravated the effect of KA-SE on AHN. In the present study, we study the role of microRNA antagonists (antagomirs) targeting miR-124 and -137 and focus on the astrocytic conversion of NSCs and the occurrence of reactive NSCs. Methods: 7 week old Nestin-GFP transgenic male mice were injected intrahippocampally with antagomirs targeting miR-124 and -137, or with non-targeting antagomirs, followed by intrahippocampal KA injections 48 hours later. In a second, more therapeutically oriented approach, animals received intrahippocampal antagomir injections 2 hours after the induction of KA-SE, as assessed behaviourally using the Racine scale. Mice were sacrificed 72 hours after KA-SE. In a second experiment, 7 week old GAD67-GFP transgenic male mice were subjected to a similar protocol. All mice were sacrificed 21 days after KA-SE. Using immunohistochemistry to identify NSCs and astrocytes and confocal microscopy we studied astrocytic conversion of NSC and gliogenesis. Results: Preliminary data indicate antagomiR-124 and -137 administration affects the rate of astrocytic conversion of NSCs, and provides a first indication of a possible new therapeutic approach to prevent aberrant AHN associated with epileptogenesis.