Co-administration of Anti microRNA-124 and -137 Oligonucleotides Prevents Hippocampal Neural Stem Cell Loss Upon Non-convulsive Seizures
Convulsive seizures promote adult hippocampal neurogenesis (AHN) through a transient activation of neural stem/progenitor cells (NSPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG). However, in a significant population of epilepsy patients, non-convulsive seizures (ncSZ) are observed. The...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2019.00031/full |
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| author | Pascal Bielefeld Marijn Schouten Guido M. Meijer Marit J. Breuk Karlijne Geijtenbeek Sedef Karayel Alisa Tiaglik Anna H. Vuuregge Ruth A.L. Willems Diede Witkamp Paul J. Lucassen Juan M. Encinas Juan M. Encinas Juan M. Encinas Carlos P. Fitzsimons |
| author_facet | Pascal Bielefeld Marijn Schouten Guido M. Meijer Marit J. Breuk Karlijne Geijtenbeek Sedef Karayel Alisa Tiaglik Anna H. Vuuregge Ruth A.L. Willems Diede Witkamp Paul J. Lucassen Juan M. Encinas Juan M. Encinas Juan M. Encinas Carlos P. Fitzsimons |
| author_sort | Pascal Bielefeld |
| collection | DOAJ |
| description | Convulsive seizures promote adult hippocampal neurogenesis (AHN) through a transient activation of neural stem/progenitor cells (NSPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG). However, in a significant population of epilepsy patients, non-convulsive seizures (ncSZ) are observed. The response of NSPCs to non-convulsive seizure induction has not been characterized before. We here studied first the short-term effects of controlled seizure induction on NSPCs fate and identity. We induced seizures of controlled intensity by intrahippocampally injecting increasing doses of the chemoconvulsant kainic acid (KA) and analyzed their effect on subdural EEG recordings, hippocampal structure, NSPC proliferation and the number and location of immature neurons shortly after seizure onset. After establishing a KA dose that elicits ncSZ, we then analyzed the effects of ncSZ on NSPC proliferation and NSC identity in the hippocampus. ncSZ specifically triggered neuroblast proliferation, but did not induce proliferation of NSPCs in the SGZ, 3 days post seizure onset. However, ncSZ induced significant changes in NSPC composition in the hippocampus, including the generation of reactive NSCs. Interestingly, intrahippocampal injection of a combination of two anti microRNA oligonucleotides targeting microRNA-124 and -137 normalized neuroblast proliferation and prevented NSC loss in the DG upon ncSZ. Our results show for the first time that ncSZ induce significant changes in neuroblast proliferation and NSC composition. Simultaneous antagonism of both microRNA-124 and -137 rescued seizure-induced alterations in NSPC, supporting their coordinated action in the regulation of NSC fate and proliferation and their potential for future seizure therapies. |
| first_indexed | 2024-12-22T15:29:50Z |
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| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-22T15:29:50Z |
| publishDate | 2019-02-01 |
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| spelling | doaj.art-1bea6e11e773429e90418b518649ae072022-12-21T18:21:23ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-02-011210.3389/fnmol.2019.00031421488Co-administration of Anti microRNA-124 and -137 Oligonucleotides Prevents Hippocampal Neural Stem Cell Loss Upon Non-convulsive SeizuresPascal Bielefeld0Marijn Schouten1Guido M. Meijer2Marit J. Breuk3Karlijne Geijtenbeek4Sedef Karayel5Alisa Tiaglik6Anna H. Vuuregge7Ruth A.L. Willems8Diede Witkamp9Paul J. Lucassen10Juan M. Encinas11Juan M. Encinas12Juan M. Encinas13Carlos P. Fitzsimons14Neuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsAchucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, Zamudio, SpainIkerbasque Foundation, Bilbao, SpainUniversity of the Basque Country (UPV/EHU), Leioa, SpainNeuroscience Program, Swammerdam Institute for Life Sciences, Faculty of Sciences, University of Amsterdam, Amsterdam, NetherlandsConvulsive seizures promote adult hippocampal neurogenesis (AHN) through a transient activation of neural stem/progenitor cells (NSPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG). However, in a significant population of epilepsy patients, non-convulsive seizures (ncSZ) are observed. The response of NSPCs to non-convulsive seizure induction has not been characterized before. We here studied first the short-term effects of controlled seizure induction on NSPCs fate and identity. We induced seizures of controlled intensity by intrahippocampally injecting increasing doses of the chemoconvulsant kainic acid (KA) and analyzed their effect on subdural EEG recordings, hippocampal structure, NSPC proliferation and the number and location of immature neurons shortly after seizure onset. After establishing a KA dose that elicits ncSZ, we then analyzed the effects of ncSZ on NSPC proliferation and NSC identity in the hippocampus. ncSZ specifically triggered neuroblast proliferation, but did not induce proliferation of NSPCs in the SGZ, 3 days post seizure onset. However, ncSZ induced significant changes in NSPC composition in the hippocampus, including the generation of reactive NSCs. Interestingly, intrahippocampal injection of a combination of two anti microRNA oligonucleotides targeting microRNA-124 and -137 normalized neuroblast proliferation and prevented NSC loss in the DG upon ncSZ. Our results show for the first time that ncSZ induce significant changes in neuroblast proliferation and NSC composition. Simultaneous antagonism of both microRNA-124 and -137 rescued seizure-induced alterations in NSPC, supporting their coordinated action in the regulation of NSC fate and proliferation and their potential for future seizure therapies.https://www.frontiersin.org/article/10.3389/fnmol.2019.00031/fullnon-convulsive seizureskainic acidadult hippocampal neurogenesisneural stem cell fatemicroRNA |
| spellingShingle | Pascal Bielefeld Marijn Schouten Guido M. Meijer Marit J. Breuk Karlijne Geijtenbeek Sedef Karayel Alisa Tiaglik Anna H. Vuuregge Ruth A.L. Willems Diede Witkamp Paul J. Lucassen Juan M. Encinas Juan M. Encinas Juan M. Encinas Carlos P. Fitzsimons Co-administration of Anti microRNA-124 and -137 Oligonucleotides Prevents Hippocampal Neural Stem Cell Loss Upon Non-convulsive Seizures Frontiers in Molecular Neuroscience non-convulsive seizures kainic acid adult hippocampal neurogenesis neural stem cell fate microRNA |
| title | Co-administration of Anti microRNA-124 and -137 Oligonucleotides Prevents Hippocampal Neural Stem Cell Loss Upon Non-convulsive Seizures |
| title_full | Co-administration of Anti microRNA-124 and -137 Oligonucleotides Prevents Hippocampal Neural Stem Cell Loss Upon Non-convulsive Seizures |
| title_fullStr | Co-administration of Anti microRNA-124 and -137 Oligonucleotides Prevents Hippocampal Neural Stem Cell Loss Upon Non-convulsive Seizures |
| title_full_unstemmed | Co-administration of Anti microRNA-124 and -137 Oligonucleotides Prevents Hippocampal Neural Stem Cell Loss Upon Non-convulsive Seizures |
| title_short | Co-administration of Anti microRNA-124 and -137 Oligonucleotides Prevents Hippocampal Neural Stem Cell Loss Upon Non-convulsive Seizures |
| title_sort | co administration of anti microrna 124 and 137 oligonucleotides prevents hippocampal neural stem cell loss upon non convulsive seizures |
| topic | non-convulsive seizures kainic acid adult hippocampal neurogenesis neural stem cell fate microRNA |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2019.00031/full |
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