title: In VivoExpression of Reprogramming Factors Increases Hippocampal Neurogenesis and Synaptic Plasticity in Chronic Hypoxic-Ischemic Brain Injury.
abstract: Neurogenesis and synaptic plasticity can be stimulatedin vivoin the brain. In this study, we hypothesized thatin vivoexpression of reprogramming factors such asKlf4,Sox2,Oct4, andc-Mycwould 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 vivoexpression 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.
authors.affiliation: Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Soohyun
authors.initials: S
authors.lastname: Wi
authors.affiliation: Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Ji Hea
authors.initials: JH
authors.lastname: Yu
authors.affiliation: Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: MinGi
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Yonsei Stem Cell Research Center, Avison Biomedical Research Center, Seoul 03722, Republic of Korea.
authors.forename: Sung-Rae
authors.identifier: 0000-0003-1429-2684
authors.initials: SR
authors.lastname: Cho
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000503:physiopathology*; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D000090062:Kruppel-Like Factor 4; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology