Intravenously Infused F3.Olig2 Improves Memory Deficits via Restoring Myelination in the Aged Hippocampus following Experimental Ischemic Stroke

Ji Hyeon Ahn; Bai Hui Chen; Bich Na Shin; Jeong Hwi Cho; In Hye Kim; Joon Ha Park; Jae Chul Lee; Hyun Jin Tae; Yun Lyul Lee; Jaesuk Lee; Kyunghee Byun; Goo-Bo Jeong; Bonghee Lee; Seung U. Kim; Young-Myeong Kim; Moo-Ho Won DVM, Ph.D.; Soo Young Choi Ph.D.

doi:10.3727/096368916X692230

Cell Transplantation (Dec 2016)

Intravenously Infused F3.Olig2 Improves Memory Deficits via Restoring Myelination in the Aged Hippocampus following Experimental Ischemic Stroke

Ji Hyeon Ahn,
Bai Hui Chen,
Bich Na Shin,
Jeong Hwi Cho,
In Hye Kim,
Joon Ha Park,
Jae Chul Lee,
Hyun Jin Tae,
Yun Lyul Lee,
Jaesuk Lee,
Kyunghee Byun,
Goo-Bo Jeong,
Bonghee Lee,
Seung U. Kim,
Young-Myeong Kim,
Moo-Ho Won DVM, Ph.D.,
Soo Young Choi Ph.D.

Affiliations

Ji Hyeon Ahn: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, South Korea
Bai Hui Chen: Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China
Bich Na Shin: Department of Physiology, College of Medicine, Institute of Neurodegeneration and Neuroregeneration, Hallym University, Chuncheon, South Korea
Jeong Hwi Cho: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea
In Hye Kim: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea
Joon Ha Park: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, South Korea
Jae Chul Lee: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea
Hyun Jin Tae: Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, South Korea
Yun Lyul Lee: Department of Histology and Embryology, Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China
Jaesuk Lee: Center for Genomics and Proteomics, Institute for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea
Kyunghee Byun: Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon, South Korea
Goo-Bo Jeong: Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon, South Korea
Bonghee Lee: Department of Anatomy and Cell Biology, Gachon University Graduate School of Medicine, Incheon, South Korea
Seung U. Kim: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Young-Myeong Kim: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, South Korea
Moo-Ho Won DVM, Ph.D.: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea
Soo Young Choi Ph.D.: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, South Korea

DOI: https://doi.org/10.3727/096368916X692230
Journal volume & issue: Vol. 25

Abstract

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Oligodendrocytes play a crucial role in creating the myelin sheath that is an important component in neural transmission. In an animal model of transient cerebral ischemia, application of oligodendrocyte progenitor cells (OPCs) has not yet been reported. In this study, the effects of F3.Olig2 transplantation on memory and cognitive dysfunction were investigated in the aged gerbil in which ischemic stroke was induced. To investigate the possible mechanisms underlying repair, changes in the expression of myelin basic protein (MBP), oligodendrocyte-specific protein (OSP), and brain-derived neurotrophic factor (BDNF) were examined. Experimental ischemic stroke was induced by occlusion of bilateral common carotid arteries in aged gerbils. Gerbils ( n = 31 per group) were randomly divided into three groups: (1) vehicle sham group, (2) vehicle ischemia group, and (3) F3.Olig2 ischemia group. After 1, 3, and 7 days of ischemia–reperfusion (I-R), saline or F3.Olig2 cells (1 × 10 6 cells in 100 μl) were injected into the gerbils intravenously. The gerbils were sacrificed 10 days after I-R for identification of grafted F3.Olig2 cells, and 15 and 30 days after I-R for tissue analysis after conducting passive avoidance and novel object recognition test. Injected F3.Olig2 cells and MBP, OSP, and BDNF were detected by specific antibodies using immunohistochemistry and/or Western blots. Memory and cognition were significantly increased in the F3.Olig2 ischemia group compared with the vehicle ischemia group. In the F3.Olig2 ischemia group, the neurons were not protected from ischemic damage; however, MBP, OSP, and BDNF expressions were significantly increased. Our results show that injection of F3.Olig2 cells significantly improved impaired memory and cognition, which might be related to increased MBP expression via increasing OSP and BDNF expression in the aged gerbil hippocampus following transient cerebral ischemia.

Published in Cell Transplantation

ISSN: 0963-6897 (Print); 1555-3892 (Online)
Publisher: SAGE Publishing
Country of publisher: United States
LCC subjects: Medicine
Website: http://journals.sagepub.com/home/cll

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