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...

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Authors: Beamer, Edward, Jurado-Arjona, Jerónimo, Jiménez-Mateos, Eva, Morgan, James, Reschke, Cristina, Kenny, Aidan, de Leo, Gioacchino, Olivos Ore, Luis Alcides, Arribas Blázquez, Marina, Madden, Stephen, Merchan-Rubira, Jesús, Delanty, Norman, Farrel, Michael A., O`Brien, Donncha, Ávila, Jesús, Díaz Hernández, Miguel, Miras Portugal, María Teresa, Rodríguez Artalejo, Antonio, Henshall, David, Engel, Tobías
Format: article
Publication Date:2018
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/95063
Online Access:https://hdl.handle.net/20.500.14352/95063
Access Level:Open access
Keyword:636.09
Status epilepticus
Epilepsy
Neurogenesis
Microrna-22
Mouse model
Veterinaria
3109 Ciencias Veterinarias
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spelling MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status EpilepticusEl microARN-22 controla la neurogénesis aberrante y los cambios en la morfología neuronal tras el estado epilépticoBeamer, EdwardJurado-Arjona, JerónimoJiménez-Mateos, EvaMorgan, JamesReschke, CristinaKenny, Aidande Leo, GioacchinoOlivos Ore, Luis AlcidesArribas Blázquez, MarinaMadden, StephenMerchan-Rubira, JesúsDelanty, NormanFarrel, Michael A.O`Brien, DonnchaÁvila, JesúsDíaz Hernández, MiguelMiras Portugal, María TeresaRodríguez Artalejo, AntonioHenshall, DavidEngel, Tobías636.09Status epilepticusEpilepsyNeurogenesisMicrorna-22Mouse modelVeterinaria3109 Ciencias VeterinariasProlonged 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 SAUniversidad Complutense de Madrid20182018-01-0120182018-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/95063reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available BFU2014-53654-P MECANISMOS PURINERGICOS IMPLICADOS EN NEUROPROTECCION Y DIFERENCIACION DE PROGENITORES NEURALESopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/950632026-06-02T12:44:21Z
dc.title.none.fl_str_mv MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus
El microARN-22 controla la neurogénesis aberrante y los cambios en la morfología neuronal tras el estado epiléptico
title MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus
spellingShingle MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus
Beamer, Edward
636.09
Status epilepticus
Epilepsy
Neurogenesis
Microrna-22
Mouse model
Veterinaria
3109 Ciencias Veterinarias
title_short 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_sort MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus
dc.creator.none.fl_str_mv Beamer, Edward
Jurado-Arjona, Jerónimo
Jiménez-Mateos, Eva
Morgan, James
Reschke, Cristina
Kenny, Aidan
de Leo, Gioacchino
Olivos Ore, Luis Alcides
Arribas Blázquez, Marina
Madden, Stephen
Merchan-Rubira, Jesús
Delanty, Norman
Farrel, Michael A.
O`Brien, Donncha
Ávila, Jesús
Díaz Hernández, Miguel
Miras Portugal, María Teresa
Rodríguez Artalejo, Antonio
Henshall, David
Engel, Tobías
author Beamer, Edward
author_facet Beamer, Edward
Jurado-Arjona, Jerónimo
Jiménez-Mateos, Eva
Morgan, James
Reschke, Cristina
Kenny, Aidan
de Leo, Gioacchino
Olivos Ore, Luis Alcides
Arribas Blázquez, Marina
Madden, Stephen
Merchan-Rubira, Jesús
Delanty, Norman
Farrel, Michael A.
O`Brien, Donncha
Ávila, Jesús
Díaz Hernández, Miguel
Miras Portugal, María Teresa
Rodríguez Artalejo, Antonio
Henshall, David
Engel, Tobías
author_role author
author2 Jurado-Arjona, Jerónimo
Jiménez-Mateos, Eva
Morgan, James
Reschke, Cristina
Kenny, Aidan
de Leo, Gioacchino
Olivos Ore, Luis Alcides
Arribas Blázquez, Marina
Madden, Stephen
Merchan-Rubira, Jesús
Delanty, Norman
Farrel, Michael A.
O`Brien, Donncha
Ávila, Jesús
Díaz Hernández, Miguel
Miras Portugal, María Teresa
Rodríguez Artalejo, Antonio
Henshall, David
Engel, Tobías
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 636.09
Status epilepticus
Epilepsy
Neurogenesis
Microrna-22
Mouse model
Veterinaria
3109 Ciencias Veterinarias
topic 636.09
Status epilepticus
Epilepsy
Neurogenesis
Microrna-22
Mouse model
Veterinaria
3109 Ciencias Veterinarias
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.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/95063
url https://hdl.handle.net/20.500.14352/95063
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available BFU2014-53654-P MECANISMOS PURINERGICOS IMPLICADOS EN NEUROPROTECCION Y DIFERENCIACION DE PROGENITORES NEURALES
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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