Age-Related Changes of Adult Neural Stem Cells in the MouseHippocampal Dentate Gyrus
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
This study was designed to investigate the changes in the properties of the neuronal setm cells or progenitor cells associated with age-related decline in neurogenesis of the hippocampal dentate gyrus (DG). Active whole cells cycle marker Ki67 (a marker of whole cell cycle)-positive and S phase marker bromodeoxyuridine (BrdU)-positive. Neural stem cells gradually were reduced in the hippocampal subgranular zone (SGZ) in an age-dependant manner after birth (from P1 month to P1 year). The ratio of BrdUpositive cells/Ki67-positive cells was gradually enhanced in an age-dependent manner. The ratio of Ki67-positive cells/ accu-mulating BrdU-positive cells at 3 hrs after BrdU injection was injected once a day for consecutive 5 days gradually decreased during ageing. TUNEL- and caspase 3 (apoptotic terminal caspase)-positive cells gradually decreased in the dentate SGZ during ageing and immunohistochemical findings of glial fibrillary acid protein (GFAP) were not changed during ageing. NeuN, a marker of mature neural cells, and BrdU-double positive cells gradually decreased in an age-dependent manner but differentiating ratio and survival rate of cells were not changed at 4 wks after BrdU injection once a day for consecutive 5 days. The number of BrdU-positive cells migrated from the hippocampal SGZ into granular layer and its migration speed was gradually declined during ageing. These results suggest that the adult neurogenesis in the mouse hippocampal DG gradually decrease through reducing proliferation of neural stem cells accompanying with cells cycle change and reduced cells migration rather than changes of differentiation.
Abstract
This study was designed to investigate the changes in the properties of the neuronal setm cells or progenitor cells associated with age-related decline in neurogenesis of the hippocampal dentate gyrus (DG). Active whole cells cycle marker Ki67 (a marker of whole cell cycle)-positive and S phase marker bromodeoxyuridine (BrdU)-positive. Neural stem cells gradually were reduced in the hippocampal subgranular zone (SGZ) in an age-dependant manner after birth (from P1 month to P1 year). The ratio of BrdUpositive cells/Ki67-positive cells was gradually enhanced in an age-dependent manner. The ratio of Ki67-positive cells/ accu-mulating BrdU-positive cells at 3 hrs after BrdU injection was injected once a day for consecutive 5 days gradually decreased during ageing. TUNEL- and caspase 3 (apoptotic terminal caspase)-positive cells gradually decreased in the dentate SGZ during ageing and immunohistochemical findings of glial fibrillary acid protein (GFAP) were not changed during ageing. NeuN, a marker of mature neural cells, and BrdU-double positive cells gradually decreased in an age-dependent manner but differentiating ratio and survival rate of cells were not changed at 4 wks after BrdU injection once a day for consecutive 5 days. The number of BrdU-positive cells migrated from the hippocampal SGZ into granular layer and its migration speed was gradually declined during ageing. These results suggest that the adult neurogenesis in the mouse hippocampal DG gradually decrease through reducing proliferation of neural stem cells accompanying with cells cycle change and reduced cells migration rather than changes of differentiation.
참고문헌 (18)
- Cameron H. A, "Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus", Neuroscience, 61, pp.203~209 (1994)
- Campisi J., "Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors", Cell, 120, pp.513~522 (2005)
- Eriksson P. S., "Neurogenesis in the adult human hippocampus", Nature Medicine, 4, pp.1313~1317 (1998)
- Gage F. H., "Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain", Proceedings of the National Academy of Sciences of the United States of America, 통권 : 92, pp.11879~11883 (1995)
- Georg K. H., "Neurogenesis in the dentate gyrus of the adult rat: Age-related decrease of neuronal progenitor proliferation", Journal of Neuroscience, 76, pp.2027~2033 (1996)
- Kempermann G., "More hippocampal neurons in adult mice living in an enriched environment", Nature, 386, pp.493~495 (1997)
- Kuhn H. G., "Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation", Journal of Neuroscience, 16, pp.2027~2033 (1996)
- Lombard D.B., "DNA repair,genome stability,and aging", Cell, 120, pp.497~512 (2005)
- Lois C., "Chain migration of neuronal precursors", Science, 271, pp.978~981 (1996)
- Magavi S. S., "Induction of neurogenesis in the neocortex of adult mice", Nature, 405, pp.951~955 (2000)
- Maslov A. Y., "Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice", Journal of Neuroscience, 24, pp.1726~1733 (2004)
- Ming G. I., "Adult neurogenesis in the mammalian central nervous system", Annual Review of Neuroscience, 28, pp.223~250 (2005)
- Molofsky A. V., "Increasing p16INK4a Expression decreases forebrain progenitors and neurogenesis during ageing", Nature, 433, pp.448~452 (2006)
- Parent J. M., "Dentate granule neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult hippocampus", Journal of Neuroscience, 17, pp.3727~3738 (1997)
- Reynolds B. A., "Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system", Science, 255, pp.1707~1710 (1992)
- Sanai N., "Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration", Nature, 427, pp.740~744 (2004)
- Seri B., "Astrocytes give rise to new neurons in the adult mammalian hippocampus", Journal of Neuroscience, 21, pp.7153~7160 (2001)
- van Praag H., "Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus", Nature Neuroscience, 2, pp.266~270 (1999)