Open AccessPromotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone
Author(s) -
Kim Joo Yeon,
Choi Kyuhyun,
Shaker Mohammed R.,
Lee JuHyun,
Lee Boram,
Lee Eunsoo,
Park JaeYong,
Lim MiSun,
Park ChangHwan,
Shin Ki Soon,
Kim Hyun,
Geum Dongho,
Sun Woong
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2276
Subject(s) - neurogenesis , neuroblast , biology , neural stem cell , neuroscience , cortex (anatomy) , subventricular zone , neocortex , cerebral cortex , stem cell , microbiology and biotechnology , anatomy
A bstract 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. S tem C ells 2016;34:888–901