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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Autores: 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., Hernández Pérez, Félix, Henshall, David C., Engel, Tobias
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/690864
Acceso en línea:http://hdl.handle.net/10486/690864
https://dx.doi.org/10.3389/fnmol.2018.00442
Access Level:acceso abierto
Palabra clave:Epilepsy
MicroRNA-22
Mouse model
Neurogenesis
Status epilepticus
Biología y Biomedicina / Biología
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network_name_str España
repository_id_str
dc.title.none.fl_str_mv 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
spellingShingle MicroRNA-22 controls aberrant neurogenesis and changes in neuronal morphology after status epilepticus
Beamer, Edward H.
Epilepsy
MicroRNA-22
Mouse model
Neurogenesis
Status epilepticus
Biología y Biomedicina / Biología
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 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.
Hernández Pérez, Félix
Henshall, David C.
Engel, Tobias
author Beamer, Edward H.
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.
Hernández Pérez, Félix
Henshall, David C.
Engel, Tobias
author_role author
author2 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.
Hernández Pérez, Félix
Henshall, David C.
Engel, Tobias
author2_role author
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 Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Epilepsy
MicroRNA-22
Mouse model
Neurogenesis
Status epilepticus
Biología y Biomedicina / Biología
topic Epilepsy
MicroRNA-22
Mouse model
Neurogenesis
Status epilepticus
Biología y Biomedicina / Biología
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
2018-12-11
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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 http://hdl.handle.net/10486/690864
https://dx.doi.org/10.3389/fnmol.2018.00442
url http://hdl.handle.net/10486/690864
https://dx.doi.org/10.3389/fnmol.2018.00442
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Framework Programme Seven 602130
European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 753527
European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 766124


dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
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
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling MicroRNA-22 controls aberrant neurogenesis and changes in neuronal morphology after status epilepticusBeamer, Edward H.Jurado-Arjona, JeronimoJimenez-Mateos, Eva M.Morgan, JamesReschke, Cristina R.Kenny, Aidande Leo, GioacchinoOlivos-Oré, Luis A.Arribas-Blázquez, MarinaMadden, Stephen F.Merchán Rubira, JesúsDelanty, NormanFarrell, Michael A.O’Brien, Donncha F.Avila, JesusDiaz-Hernandez, MiguelMiras-Portugal, M. TeresaArtalejo, Antonio R.Hernández Pérez, FélixHenshall, David C.Engel, TobiasEpilepsyMicroRNA-22Mouse modelNeurogenesisStatus epilepticusBiología y Biomedicina / BiologíaProlonged 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 SEThis work was supported by funding from Science Foundation Ireland (13/SIRG/2098, 17/CDA/4708 and 16/TIDA/4059 to TE, 13/SIRG/2114 to EJ-M, 17/TIDA/5002 to CR, 13/IA/1891 and 16/RC/3948 to DH and co-funded under the European Regional Development Fund and by FutureNeuro Industry partners) from the Health Research Board (HRA-POR-2015-1243 to TE), from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n◦ 602130 (to DH), from the H2020 Marie Skłowdowksa-Curie Actions Individual Fellowship (753527 to EB), from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement (No 766124 to TE), S2013/ICE-2958 from Comunidad de Madrid to MM-P, from Fundación ‘‘La Caixa’’ to JM-R and from Areces Foundation C-XVIII and the Minister of Science and Universities of Spain BFU2014-53654-P to MM-PFrontiers Research FoundationDepartamento de Biología MolecularFacultad de Ciencias20182018-12-11research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/690864https://dx.doi.org/10.3389/fnmol.2018.00442reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Framework Programme Seven 602130European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 753527European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 766124open accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6908642026-06-23T12:46:27Z
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