論文 - 島崎　琢也

Current understanding of adult neurogenesis in the mammalian brain: How does adult neurogenesis decrease with age?

Kase Y., Kase Y., Shimazaki T., Okano H.

Inflammation and Regeneration （Inflammation and Regeneration）  40 （ 1 ）  2020年06月

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© 2020 The Author(s). Adult neurogenesis occurs throughout life in restricted brain regions in mammals. However, the number of neural stem cells (NSCs) that generate new neurons steadily decreases with age, resulting in a decrease in neurogenesis. Transplantation of mesenchymal cells or cultured NSCs has been studied as a promising treatment in models of several brain injuries including cerebral infarction and cerebral contusion. Considering the problems of host-versus-graft reactions and the tumorigenicity of transplanted cells, the mobilization of endogenous adult NSCs should be more feasible for the treatment of these brain injuries. However, the number of adult NSCs in the adult brain is limited, and their mitotic potential is low. Here, we outline what we know to date about why the number of NSCs and adult neurogenesis decrease with age. We also discuss issues applicable to regenerative medicine.

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Involvement of p38 in Age-Related Decline in Adult Neurogenesis via Modulation of Wnt Signaling

Kase Y., Otsu K., Shimazaki T., Okano H.

Stem Cell Reports （Stem Cell Reports）  12 （ 6 ） 1313 - 1328 2019年06月

ISSN  22136711

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© 2019 The Author(s) Neurogenesis in specific brain regions in adult mammals decreases with age. Progressive reduction in the proliferation of neural stem and progenitor cells (NS/PCs) is a primary cause of this age-associated decline. However, the mechanism responsible for this reduction is poorly understood. We identify p38 MAPK as a key factor in the proliferation of neural progenitor cells (NPCs) in adult neurogenic niches. p38 expression in adult NS/PCs is downregulated during aging. Deletion of p38α in NS/PCs specifically reduces the proliferation of NPCs but not stem cells. Conversely, forced expression of p38α in NS/PCs in the aged mouse subventricular zone (SVZ) restores NPC proliferation and neurogenesis, and prevents age-dependent SVZ atrophy. We also found that p38 is necessary for suppressing the expression of Wnt antagonists DKK1 and SFRP3, which inhibit the proliferation of NPCs. Age-related reduction in p38 thus leads to decreased adult neurogenesis via downregulation of Wnt signaling. Kase et al. show that p38 expression in neural stem and progenitor cells (NS/PCs) in the adult brain decreases with aging. This reduction specifically causes proliferation defect in neural progenitor cells (NPCs), leading to the age-dependent decline of adult neurogenesis. Conversely, overexpression of p38α in NS/PCs in the aged brain restores NPC proliferation without exhaustion of neural stem cells.

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Vertebrate Neural Stem cells: Development, Plasticity and Regeneration.

島崎 琢也

The Keio Journal of Medicine 65 （ 1 ） 1 - 15 2016年02月

研究論文（学術雑誌）, 単著, 査読有り

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Heterochronic microRNAs in temporal specification of neural stem cells: application toward rejuvenation.

島崎 琢也

NPJ Aging and Mechanisms of Diseases 2   15014 2016年01月

研究論文（学術雑誌）, 共著, 査読有り

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MicroRNA-153 Regulates the Acquisition of Gliogenic Competence by Neural Stem Cells

島崎 琢也

Stem Cell Reports 5 （ 3 ） 365 - 377 2015年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2213-6711

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LIM Homeobox 8 (Lhx8) Is a Key Regulator of the Cholinergic Neuronal Function via a Tropomyosin Receptor Kinase A (TrkA)-mediated Positive Feedback Loop

島崎 琢也

JOURNAL OF BIOLOGICAL CHEMISTRY 289 （ 2 ） 1000 - 1010 2014年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0021-9258

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The miR-17/106-p38 axis is a key regulator of the neurogenic-to-gliogenic transition in developing neural stem/progenitor cells

島崎 琢也

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111 （ 4 ） 1604 - 1609 2014年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0027-8424

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FRS2 alpha Regulates Erk Levels to Control a Self-Renewal Target Hes1 and Proliferation of FGF-Responsive Neural Stem/Progenitor Cells

島崎 琢也

STEM CELLS 28 （ 9 ） 1660 - 1672 2010年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1066-5099

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Regulation of adult neural progenitor cells by Galectin-1/beta 1 Integrin interaction

島崎 琢也

JOURNAL OF NEUROCHEMISTRY 113 （ 6 ） 1516 - 1524 2010年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0022-3042

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Stromal Cell-Secreted Factors Promote the Survival of Embryonic Stem Cell-Derived Early Neural Stem/Progenitor Cells Via the Activation of MAPK and PI3K-Akt Pathways

島崎 琢也

JOURNAL OF NEUROSCIENCE RESEARCH 88 （ 4 ） 722 - 734 2010年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0360-4012

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Efficient Generation of Mature Cerebellar Purkinje Cells From Mouse Embryonic Stem Cells

島崎 琢也

JOURNAL OF NEUROSCIENCE RESEARCH 88 （ 2 ） 234 - 247 2010年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0360-4012

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Evaluation of Human Fetal Neural Stem/Progenitor Cells as a Source for Cell Replacement Therapy for Neurological Disorders: Properties and Tumorigenicity After Long-Term In Vitro Maintenance

島崎 琢也

JOURNAL OF NEUROSCIENCE RESEARCH 87 （ 2 ） 307 - 317 2009年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0360-4012

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Requirement for COUP-TFI and II in the temporal specification of neural stem cells in CNS development

島崎 琢也

NATURE NEUROSCIENCE 11 （ 9 ） 1014 - 1023 2008年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1097-6256

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Roles of STAT3/SOCS3 pathway in regulating the visual function and ubiquitin-proteasome-dependent degradation of rhodopsin during retinal inflammation

島崎 琢也

JOURNAL OF BIOLOGICAL CHEMISTRY 283 （ 36 ） 24561 - 24570 2008年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0021-9258

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Consequence of the loss of Sox2 in the developing brain of the mouse

島崎 琢也

FEBS LETTERS 582 （ 18 ） 2811 - 2815 2008年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0014-5793

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Spatiotemporal Recapitulation of Central Nervous System Development by Murine Embryonic Stem Cell-Derived Neural Stem/Progenitor Cells

島崎 琢也

STEM CELLS 26 （ 12 ） 3086 - 3098 2008年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1066-5099

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Epidermal growth factor signaling mediated by Grb2 associated binder1 is required for the spatiotemporally regulated proliferation of Olig2-expressing progenitors in the embryonic spinal cord

島崎 琢也

STEM CELLS 25 （ 6 ） 1410 - 1422 2007年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1066-5099

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Leptin suppresses ghrelin-induced activation of neuropeptide y neurons in the arcuate nucleus via phosphatidylinositol 3-kinase- and phosphodiesterase 3-mediated pathway

島崎 琢也

ENDOCRINOLOGY 148 （ 5 ） 2251 - 2263 2007年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0013-7227

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SOCS3 is required to temporally fine-tune photoreceptor cell differentiation

島崎 琢也

DEVELOPMENTAL BIOLOGY 303 （ 2 ） 591 - 600 2007年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0012-1606

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Simian fetal brain progenitor cells for studying viral neuropathogenesis

島崎 琢也

JOURNAL OF NEUROVIROLOGY 13 （ 1 ） 11 - 22 2007年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1355-0284

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