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Neural Plasticity
Volume 2016, Article ID 2580837, 11 pages
http://dx.doi.org/10.1155/2016/2580837
Research Article

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

Soohyun Wi,1,2 Ji Hea Yu,1,2 MinGi Kim,1,2 and Sung-Rae Cho1,2,3,4

1Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
2Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
3Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
4Yonsei Stem Cell Research Center, Avison Biomedical Research Center, Seoul 03722, Republic of Korea

Received 17 June 2016; Revised 25 August 2016; Accepted 21 September 2016

Academic Editor: Yong Jeong

Copyright © 2016 Soohyun Wi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.