RT Journal Article
T1 MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus
T2 El microARN-22 controla la neurogénesis aberrante y los cambios en la morfología neuronal tras el estado epiléptico
A1 Beamer, Edward
A1 Jurado-Arjona, Jerónimo
A1 Jiménez-Mateos, Eva
A1 Morgan, James
A1 Reschke, Cristina
A1 Kenny, Aidan
A1 de Leo, Gioacchino
A1 Olivos Ore, Luis Alcides
A1 Arribas Blázquez, Marina
A1 Madden, Stephen
A1 Merchan-Rubira, Jesús
A1 Delanty, Norman
A1 Farrel, Michael A.
A1 O`Brien, Donncha
A1 Ávila, Jesús
A1 Díaz Hernández, Miguel
A1 Miras Portugal, María Teresa
A1 Rodríguez Artalejo, Antonio
A1 Henshall, David
A1 Engel, Tobías
AB Prolonged seizures (status epilepticus, SE) may drive hippocampal dysfunction and epileptogenesis, at least partly, through an elevation in neurogenesis, dysregulation of migration and aberrant dendritic arborization of newly-formed neurons. MicroRNA-22 was recently found to protect against the development of epileptic foci, but the mechanisms remain incompletely understood. Here, we investigated the contribution of microRNA-22 to SE-induced aberrant adult neurogenesis. SE was induced by intraamygdala microinjection of kainic acid (KA) to model unilateral hippocampal neuropathology in mice. MicroRNA-22 expression was suppressed using specific oligonucleotide inhibitors (antagomir-22) and newly-formed neurons were visualized using the thymidine analog iodo-deoxyuridine (IdU) and a green fluorescent protein (GFP)-expressing retrovirus to visualize the dendritic tree and synaptic spines. Using this approach, we quantified differences in the rate of neurogenesis and migration, the structure of the apical dendritic tree and density and morphology of dendritic spines in newly-formed neurons. SE resulted in an increased rate of hippocampal neurogenesis, including within the undamaged contralateral dentate gyrus (DG). Newly-formed neurons underwent aberrant migration, both within the granule cell layer and into ectopic sites. Inhibition of microRNA-22 exacerbated these changes. The dendritic diameter and the density and average volume of dendritic spines were unaffected by SE, but these parameters were all elevated in mice in which microRNA-22 was suppressed. MicroRNA-22 inhibition also reduced the length and complexity of the dendritic tree, independently of SE. These data indicate that microRNA-22 is an important regulator of morphogenesis of newly-formed neurons in adults and plays a role in supressing aberrant neurogenesis associated with SE.
PB Frontiers Media SA
SN 1662-5099
YR 2018
FD 2018-11-21
LK https://hdl.handle.net/20.500.14352/95063
UL https://hdl.handle.net/20.500.14352/95063
LA eng
NO Beamer, Edward H., Jurado-Arjona, J., Jiménez-Mateos, E. et al. «MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus». Frontiers in Molecular Neuroscience, vol. 11, diciembre de 2018, p. 442. DOI.org (Crossref), https://doi.org/10.3389/fnmol.2018.00442.
NO AUTHOR CONTRIBUTIONSEB performed immunohistochemistry, contributed to data analysis and wrote the article. JJ-A performed injections of viral vectors, contributed to data analysis and edited the manuscript. EJ-M and AK performed in situ hybridization. JM and JM-R performed immunohistochemistry. CR performed immunohistochemistry and contributed to data analysis. GL carried out P2X7 immunohistochemistry. LO-O and MA-B performed patch-clamp recordings. SM performed statistical analysis. ND, MF, JJ-A, MM-P, AA and JA edited the manuscript. DO’B provided human brain sample. MD-H edited the manuscript and helped with virus injection. FH provided antibodies and edited the manuscript. DH wrote parts of the manuscript and edited the manuscript. TE performed KA injections and wrote the manuscript.
NO Science Foundation Ireland
NO European Regional Development Fund and by FutureNeuro Industry partners from the Health Research Board 
NO European Union Seventh Framework Programme
NO H2020 Marie Skłowdowksa-Curie Actions
NO Comunidad de Madrid
NO Fundación Ramón Areces
NO Fundación La Caixa
NO Ministerio de Ciencia y Universidades
DS Docta Complutense
RD 17 abr 2025