caa a22 4500 606202498 CHVBK 20210128100953.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00429-014-0798-5 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0798-5 Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus [Elektronische Daten] [Eva Jimenez-Mateos, Tobias Engel, Paula Merino-Serrais, Isabel Fernaud-Espinosa, Natalia Rodriguez-Alvarez, James Reynolds, Cristina Reschke, Ronan Conroy, Ross McKiernan, Javier deFelipe, David Henshall] Emerging data support roles for microRNA (miRNA) in the pathogenesis of various neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in dendrites of hippocampal neurons, where it negatively regulates spine volume. Recent work identified upregulation of miR-134 in experimental and human epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant effects against kainic acid-induced seizures and was associated with a reduction in dendritic spine number. In the present study, we measured dendritic spine volume in mice injected with miR-134-targeting antagomirs and tested effects of the antagomirs on status epilepticus triggered by the cholinergic agonist pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice given antagomirs compared to controls that received a scrambled sequence. Treatment of mice with miR-134 antagomirs did not alter performance in a behavioral test (novel object location). Status epilepticus induced by pilocarpine was associated with upregulation of miR-134 within the hippocampus of mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of animals that developed status epilepticus following pilocarpine and increased animal survival. In antagomir-treated mice that did develop status epilepticus, seizure onset was delayed and total seizure power was reduced. These studies provide in vivo evidence that miR-134 regulates spine volume in the hippocampus and validation of the seizure-suppressive effects of miR-134 antagomirs in a model with a different triggering mechanism, indicating broad conservation of anticonvulsant effects. Springer-Verlag Berlin Heidelberg, 2014 Anticonvulsant nationallicence Hippocampal sclerosis nationallicence Non-coding RNA nationallicence RNA-induced silencing complex nationallicence Status epilepticus nationallicence Temporal lobe epilepsy nationallicence Jimenez-Mateos Eva Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut Engel Tobias Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut Merino-Serrais Paula Laboratorio Cajal de Circuitos Corticales (CTB), Instituto Cajal (CSIC) and CIBERNED, Universidad Politécnica de Madrid, Madrid, Spain aut Fernaud-Espinosa Isabel Laboratorio Cajal de Circuitos Corticales (CTB), Instituto Cajal (CSIC) and CIBERNED, Universidad Politécnica de Madrid, Madrid, Spain aut Rodriguez-Alvarez Natalia Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut Reynolds James Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut Reschke Cristina Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut Conroy Ronan Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland aut McKiernan Ross Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut deFelipe Javier Laboratorio Cajal de Circuitos Corticales (CTB), Instituto Cajal (CSIC) and CIBERNED, Universidad Politécnica de Madrid, Madrid, Spain aut Henshall David Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2387-2399 1863-2653 220:4<2387 2015 220 429 https://doi.org/10.1007/s00429-014-0798-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0798-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jimenez-Mateos Eva Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut NATIONALLICENCE 700 1- Engel Tobias Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut NATIONALLICENCE 700 1- Merino-Serrais Paula Laboratorio Cajal de Circuitos Corticales (CTB), Instituto Cajal (CSIC) and CIBERNED, Universidad Politécnica de Madrid, Madrid, Spain aut NATIONALLICENCE 700 1- Fernaud-Espinosa Isabel Laboratorio Cajal de Circuitos Corticales (CTB), Instituto Cajal (CSIC) and CIBERNED, Universidad Politécnica de Madrid, Madrid, Spain aut NATIONALLICENCE 700 1- Rodriguez-Alvarez Natalia Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut NATIONALLICENCE 700 1- Reynolds James Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut NATIONALLICENCE 700 1- Reschke Cristina Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut NATIONALLICENCE 700 1- Conroy Ronan Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland aut NATIONALLICENCE 700 1- McKiernan Ross Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut NATIONALLICENCE 700 1- deFelipe Javier Laboratorio Cajal de Circuitos Corticales (CTB), Instituto Cajal (CSIC) and CIBERNED, Universidad Politécnica de Madrid, Madrid, Spain aut NATIONALLICENCE 700 1- Henshall David Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2387-2399 1863-2653 220:4<2387 2015 220 429