title: Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.
abstract: Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy.
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Biology, Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kyuhyun
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Shaker
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Eunsoo
authors.initials: E
authors.lastname: Lee
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Graduate School of Biomedical Science and Engineering.|Hanyang Biomedical Research Institute.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Lim
authors.affiliation: Graduate School of Biomedical Science and Engineering.|Hanyang Biomedical Research Institute.|Department of Microbiology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Park
authors.affiliation: Department of Biology, Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Ki Soon
authors.initials: KS
authors.lastname: Shin
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea.
authors.forename: Dongho
authors.initials: D
authors.lastname: Geum
authors.affiliation: Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
mesh_terms: D053687:Adult Stem Cells / Q000637:transplantation; D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000637:transplantation*; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000473:pathology; D017397:Prefrontal Cortex
keywords: Adult neural stem cells; Adult neurogenesis; Bcl-xL; Brain-derived neurotropic factor; Subcallosal zone; Traumatic brain injury