Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy
Introduction: Cerebral ischemia is the third cause of death risk in Colombia and the first cause of physical disability worldwide. Different studies on the silencing of the cyclin-dependent kinase 5 (CDK5) have shown that reducing its activity is beneficial in ischemic contexts. However, its effect...
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| Format: | Article |
| Language: | English |
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Instituto Nacional de Salud
2018-09-01
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| Series: | Biomédica: revista del Instituto Nacional de Salud |
| Subjects: | |
| Online Access: | https://www.revistabiomedica.org/index.php/biomedica/article/view/3800 |
| _version_ | 1811220228184473600 |
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| author | Juan Ignacio Muñoz-Manco Johanna Andrea Gutiérrez-Vargas Gloria Patricia Cardona-Gómez |
| author_facet | Juan Ignacio Muñoz-Manco Johanna Andrea Gutiérrez-Vargas Gloria Patricia Cardona-Gómez |
| author_sort | Juan Ignacio Muñoz-Manco |
| collection | DOAJ |
| description | Introduction: Cerebral ischemia is the third cause of death risk in Colombia and the first cause of physical disability worldwide. Different studies on the silencing of the cyclin-dependent kinase 5 (CDK5) have shown that reducing its activity is beneficial in ischemic contexts. However, its effect on neural cell production after cerebral ischemia has not been well studied yet.
Objective: To evaluate CDK5 silencing on the production of neurons and astrocytes after a focal cerebral ischemia in rats.
Materials and methods: We used 40 eight-week-old male Wistar rats. Both sham and ischemia groups were transduced at CA1 hippocampal region with an adeno-associated viral vector using a noninterfering (shSCRmiR) and an interfering sequence for CDK5 (shCDK5miR). We injected 50 mg/kg of bromodeoxyuridine intraperitoneally from hour 24 to day 7 post-ischemia. We assessed the neurological abilities during the next 15 days and we measured the immunoreactivity of bromodeoxyuridine (BrdU),
doublecortin (DCX), NeuN, and glial fibrillary acid protein (GFAP) from day 15 to day 30 post-ischemia.
Results: Our findings showed that CDK5miR-treated ischemic animals improved their neurological score and presented increased BrdU+ cells 15 days after ischemia, which correlated with higher DCX and lower GFAP fluorescence intensities, and, although mature neurons populations did not change, GFAP immunoreactivity was still significantly reduced at 30 days post-ischemia in comparison with untreated ischemic groups.
Conclusion: CDK5miR therapy generated the neurological recovery of ischemic rats associated with the induction of immature neurons proliferation and the reduction of GFAP reactivity at short and longterm post-ischemia. |
| first_indexed | 2024-04-12T07:39:09Z |
| format | Article |
| id | doaj.art-ac697ea40c044d7e9f37868274b2d3cf |
| institution | Directory Open Access Journal |
| issn | 0120-4157 0120-4157 |
| language | English |
| last_indexed | 2024-04-12T07:39:09Z |
| publishDate | 2018-09-01 |
| publisher | Instituto Nacional de Salud |
| record_format | Article |
| series | Biomédica: revista del Instituto Nacional de Salud |
| spelling | doaj.art-ac697ea40c044d7e9f37868274b2d3cf2022-12-22T03:41:52ZengInstituto Nacional de SaludBiomédica: revista del Instituto Nacional de Salud0120-41570120-41572018-09-0138338839710.7705/biomedica.v38i4.38002149Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapyJuan Ignacio Muñoz-Manco0Johanna Andrea Gutiérrez-Vargas1Gloria Patricia Cardona-Gómez2Grupo de Neurociencias de Antioquia, Área de Neurobiología Celular y Molecular, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGrupo de Neurociencias de Antioquia, Área de Neurobiología Celular y Molecular, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGrupo de Neurociencias de Antioquia, Área de Neurobiología Celular y Molecular, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaIntroduction: Cerebral ischemia is the third cause of death risk in Colombia and the first cause of physical disability worldwide. Different studies on the silencing of the cyclin-dependent kinase 5 (CDK5) have shown that reducing its activity is beneficial in ischemic contexts. However, its effect on neural cell production after cerebral ischemia has not been well studied yet. Objective: To evaluate CDK5 silencing on the production of neurons and astrocytes after a focal cerebral ischemia in rats. Materials and methods: We used 40 eight-week-old male Wistar rats. Both sham and ischemia groups were transduced at CA1 hippocampal region with an adeno-associated viral vector using a noninterfering (shSCRmiR) and an interfering sequence for CDK5 (shCDK5miR). We injected 50 mg/kg of bromodeoxyuridine intraperitoneally from hour 24 to day 7 post-ischemia. We assessed the neurological abilities during the next 15 days and we measured the immunoreactivity of bromodeoxyuridine (BrdU), doublecortin (DCX), NeuN, and glial fibrillary acid protein (GFAP) from day 15 to day 30 post-ischemia. Results: Our findings showed that CDK5miR-treated ischemic animals improved their neurological score and presented increased BrdU+ cells 15 days after ischemia, which correlated with higher DCX and lower GFAP fluorescence intensities, and, although mature neurons populations did not change, GFAP immunoreactivity was still significantly reduced at 30 days post-ischemia in comparison with untreated ischemic groups. Conclusion: CDK5miR therapy generated the neurological recovery of ischemic rats associated with the induction of immature neurons proliferation and the reduction of GFAP reactivity at short and longterm post-ischemia.https://www.revistabiomedica.org/index.php/biomedica/article/view/3800Brain ischemianeurogenesiscyclin-dependent kinase 5 |
| spellingShingle | Juan Ignacio Muñoz-Manco Johanna Andrea Gutiérrez-Vargas Gloria Patricia Cardona-Gómez Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy Biomédica: revista del Instituto Nacional de Salud Brain ischemia neurogenesis cyclin-dependent kinase 5 |
| title | Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy |
| title_full | Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy |
| title_fullStr | Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy |
| title_full_unstemmed | Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy |
| title_short | Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy |
| title_sort | neurogenesis and gliogenesis modulation in cerebral ischemia by cdk5 rnai based therapy |
| topic | Brain ischemia neurogenesis cyclin-dependent kinase 5 |
| url | https://www.revistabiomedica.org/index.php/biomedica/article/view/3800 |
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