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In Vivo Expression of Reprogramming Factors Increases Hippocampal Neurogenesis and Synaptic Plasticity in Chronic Hypoxic-Ischemic Brain Injury

Authors
 Soohyun Wi  ;  Ji Hea Yu  ;  MinGi Kim  ;  Sung-Rae Cho 
Citation
 NEURAL PLASTICITY, Vol.2016 : 2580837, 2016 
Journal Title
 NEURAL PLASTICITY 
ISSN
 2090-5904 
Issue Date
2016
MeSH
Animals ; Cell Differentiation/physiology ; Disease Models, Animal ; Hippocampus/physiopathology* ; Hypoxia-Ischemia, Brain/physiopathology* ; Memory, Long-Term/physiology* ; Mice ; Neurogenesis/physiology* ; Neuronal Plasticity/physiology* ; Recovery of Function/physiology
Abstract
Neurogenesis and synaptic plasticity can be stimulated in vivo in the brain. In this study, we hypothesized that in vivo expression of reprogramming factors such as Klf4, Sox2, Oct4, and c-Myc would facilitate endogenous neurogenesis and functional recovery. CD-1® mice were induced at 1 week of age by unilaterally carotid artery ligation and exposure to hypoxia. At 6 weeks of age, mice were injected GFP only or both four reprogramming factors and GFP into lateral ventricle. Passive avoidance task and open field test were performed to evaluate neurobehavioral function. Neurogenesis and synaptic activity in the hippocampus were evaluated using immunohistochemistry, qRT-PCR, and/or western blot analyses. Whereas BrdU+GFAP+ cells in the subgranular zone of the hippocampus were not significantly different, the numbers of BrdU+βIII-tubulin+ and BrdU+NeuN+ cells were significantly higher in treatment group than control group. Expressions of synaptophysin and PSD-95 were also higher in treatment group than control group. Importantly, passive avoidance task and open field test showed improvement in long-term memory and decreased anxiety in treatment group. In conclusion, in vivo expression of reprogramming factors improved behavioral functions in chronic hypoxic-ischemic brain injury. The mechanisms underlying these repair processes included endogenous neurogenesis and synaptic plasticity in the hippocampus.
Files in This Item:
T201604462.pdf Download
DOI
10.1155/2016/2580837
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실) > 1. Journal Papers
Yonsei Authors
Yu, Ji Hea(유지혜)
Cho, Sung-Rae(조성래) ORCID logo https://orcid.org/0000-0003-1429-2684
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152493
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