Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy

Juan Ignacio Muñoz-Manco, Johanna Andrea Gutiérrez-Vargas, Gloria Patricia Cardona-Gómez, .

DOI: https://doi.org/10.7705/biomedica.v38i4.3800
Keywords: Brain ischemia, neurogenesis, cyclin-dependent kinase 5
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Abstract

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.

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  • Juan Ignacio Muñoz-Manco Grupo de Neurociencias de Antioquia, Área de Neurobiología Celular y Molecular, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
  • Johanna Andrea Gutiérrez-Vargas Grupo de Neurociencias de Antioquia, Área de Neurobiología Celular y Molecular, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
  • Gloria Patricia Cardona-Gómez Grupo de Neurociencias de Antioquia, Área de Neurobiología Celular y Molecular, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia

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How to Cite
1.
Muñoz-Manco JI, Gutiérrez-Vargas JA, Cardona-Gómez GP. Neurogenesis and gliogenesis modulation in cerebral ischemia by CDK5 RNAi-based therapy. biomedica [Internet]. 2018 Sep. 1 [cited 2024 May 17];38(3):388-97. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/3800
Published
2018-09-01
Issue
Vol. 38 No. 3 (2018)
Section
Original articles

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