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MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus
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 deve...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298134/ https://www.ncbi.nlm.nih.gov/pubmed/30618601 http://dx.doi.org/10.3389/fnmol.2018.00442 |
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author | Beamer, Edward H. Jurado-Arjona, Jeronimo Jimenez-Mateos, Eva M. Morgan, James Reschke, Cristina R. Kenny, Aidan de Leo, Gioacchino Olivos-Oré, Luis A. Arribas-Blázquez, Marina Madden, Stephen F. Merchán-Rubira, Jesús Delanty, Norman Farrell, Michael A. O’Brien, Donncha F. Avila, Jesus Diaz-Hernandez, Miguel Miras-Portugal, M. Teresa Artalejo, Antonio R. Hernandez, Felix Henshall, David C. Engel, Tobias |
author_facet | Beamer, Edward H. Jurado-Arjona, Jeronimo Jimenez-Mateos, Eva M. Morgan, James Reschke, Cristina R. Kenny, Aidan de Leo, Gioacchino Olivos-Oré, Luis A. Arribas-Blázquez, Marina Madden, Stephen F. Merchán-Rubira, Jesús Delanty, Norman Farrell, Michael A. O’Brien, Donncha F. Avila, Jesus Diaz-Hernandez, Miguel Miras-Portugal, M. Teresa Artalejo, Antonio R. Hernandez, Felix Henshall, David C. Engel, Tobias |
author_sort | Beamer, Edward H. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6298134 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62981342019-01-07 MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus Beamer, Edward H. Jurado-Arjona, Jeronimo Jimenez-Mateos, Eva M. Morgan, James Reschke, Cristina R. Kenny, Aidan de Leo, Gioacchino Olivos-Oré, Luis A. Arribas-Blázquez, Marina Madden, Stephen F. Merchán-Rubira, Jesús Delanty, Norman Farrell, Michael A. O’Brien, Donncha F. Avila, Jesus Diaz-Hernandez, Miguel Miras-Portugal, M. Teresa Artalejo, Antonio R. Hernandez, Felix Henshall, David C. Engel, Tobias Front Mol Neurosci Neuroscience 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. Frontiers Media S.A. 2018-12-11 /pmc/articles/PMC6298134/ /pubmed/30618601 http://dx.doi.org/10.3389/fnmol.2018.00442 Text en Copyright © 2018 Beamer, Jurado-Arjona, Jimenez-Mateos, Morgan, Reschke, Kenny, de Leo, Olivos-Oré, Arribas-Blázquez, Madden, Merchán-Rubira, Delanty, Farrell, O’Brien, Avila, Diaz-Hernandez, Miras-Portugal, Artalejo, Hernandez, Henshall and Engel. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Beamer, Edward H. Jurado-Arjona, Jeronimo Jimenez-Mateos, Eva M. Morgan, James Reschke, Cristina R. Kenny, Aidan de Leo, Gioacchino Olivos-Oré, Luis A. Arribas-Blázquez, Marina Madden, Stephen F. Merchán-Rubira, Jesús Delanty, Norman Farrell, Michael A. O’Brien, Donncha F. Avila, Jesus Diaz-Hernandez, Miguel Miras-Portugal, M. Teresa Artalejo, Antonio R. Hernandez, Felix Henshall, David C. Engel, Tobias MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus |
title | MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus |
title_full | MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus |
title_fullStr | MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus |
title_full_unstemmed | MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus |
title_short | MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus |
title_sort | microrna-22 controls aberrant neurogenesis and changes in neuronal morphology after status epilepticus |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298134/ https://www.ncbi.nlm.nih.gov/pubmed/30618601 http://dx.doi.org/10.3389/fnmol.2018.00442 |
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