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: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| 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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España |
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| 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 |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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1869423961145606144 |
| 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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15,300719 |