|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
doi: 10.1242/10.1242/dev.00203
DEVELOPMENT AND DISEASE |
1 Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch,
Robert-Rössle-Str. 10, 13125 Berlin, Germany
2 VolkswagenStiftung Research Group, Dept. of Experimental Neurology,
Charité University Hospital, Humboldt University, Schumannstr. 20/21,
10117 Berlin, Germany
3 Department of Psychiatry, Freie Universität Berlin, Eschenallee 3, 14050
Berlin, Germany
4 Department of Physiology, Graduate School of Medicine, University of Tokyo,
Bunkyo-ku, Tokyo 113-0033, Japan
5 The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North
Torrey Pines Rd., La Jolla, CA 92037, USA
* Author for correspondence (e-mail: gerd.kempermann{at}mdc-berlin.de)
Accepted 11 October 2002
New neurons are continually generated in the adult hippocampus, but the important question, whether adult neurogenesis is transient or leads to the lasting presence of new neurons, has not yet been answered. Dividing cells were labeled with bromodeoxyuridine (BrdU) and were investigated by means of immunofluorescence and confocal microscopy at several time-points 1 day to 11 months thereafter. BrdU-labeled neurons remained stable in number and in their relative position in the granule cell layer over at least 11 months. This finding implies that the addition of new neurons is not transient and that their final number and localization are determined early. By contrast, expression of immature markers ß-III-tubulin and doublecortin in BrdU-labeled cells, peaked early after division and was not detectable after 4 weeks. In transgenic mice expressing enhanced green fluorescent protein under the nestin promoter none of the BrdU/nestin-positive cells early after division expressed the mature marker NeuN, confirming that no dividing neurons were detected. These new data suggest that new neurons are recruited early from the pool of proliferating progenitor cells and lead to a lasting effect of adult neurogenesis.
Key words: Stem cell, Progenitor cell, Adult neurogenesis, Mouse
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Jagasia, K. Steib, E. Englberger, S. Herold, T. Faus-Kessler, M. Saxe, F. H. Gage, H. Song, and D. C. Lie GABA-cAMP Response Element-Binding Protein Signaling Regulates Maturation and Survival of Newly Generated Neurons in the Adult Hippocampus J. Neurosci., June 24, 2009; 29(25): 7966 - 7977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Attardo, K. Fabel, J. Krebs, W. Haubensak, W. B. Huttner, and G. Kempermann Tis21 Expression Marks Not Only Populations of Neurogenic Precursor Cells but Also New Postmitotic Neurons in Adult Hippocampal Neurogenesis Cereb Cortex, May 29, 2009; (2009) bhp100v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Singh, S. Gupta, Y. Jiang, M. Younus, and M. Ramzan In vitro Neurogenesis from Neural Progenitor Cells Isolated from the Hippocampus Region of the Brain of Adult Rats Exposed to Ethanol during Early Development through Their Alcohol-Drinking Mothers Alcohol Alcohol., March 1, 2009; 44(2): 185 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jessberger, R. E. Clark, N. J. Broadbent, G. D. Clemenson Jr, A. Consiglio, D. C. Lie, L. R. Squire, and F. H. Gage Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats Learn. Mem., January 29, 2009; 16(2): 147 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-S. Yu, G. Zhang, D. J. Liebl, and S. G. Kernie Traumatic Brain Injury-Induced Hippocampal Neurogenesis Requires Activation of Early Nestin-Expressing Progenitors J. Neurosci., November 26, 2008; 28(48): 12901 - 12912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Lagace, D. R. Benavides, J. W. Kansy, M. Mapelli, P. Greengard, J. A. Bibb, and A. J. Eisch Cdk5 is essential for adult hippocampal neurogenesis PNAS, November 25, 2008; 105(47): 18567 - 18571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Walzlein, M. Synowitz, B. Engels, D. S. Markovic, K. Gabrusiewicz, E. Nikolaev, K. Yoshikawa, B. Kaminska, G. Kempermann, W. Uckert, et al. The Antitumorigenic Response of Neural Precursors Depends on Subventricular Proliferation and Age Stem Cells, November 1, 2008; 26(11): 2945 - 2954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Danzer Postnatal and Adult Neurogenesis in the Development of Human Disease Neuroscientist, October 1, 2008; 14(5): 446 - 458. [Abstract] [PDF]
|
|
|
|
|
|
L. Bernardino, F. Agasse, B. Silva, R. Ferreira, S. Grade, and J. O. Malva Tumor Necrosis Factor-{alpha} Modulates Survival, Proliferation, and Neuronal Differentiation in Neonatal Subventricular Zone Cell Cultures Stem Cells, September 1, 2008; 26(9): 2361 - 2371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Koehl, P. Meerlo, D. Gonzales, A. Rontal, F. W. Turek, and D. N. Abrous Exercise-induced promotion of hippocampal cell proliferation requires {beta}-endorphin FASEB J, July 1, 2008; 22(7): 2253 - 2262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Garza, M. Guo, W. Zhang, and X.-Y. Lu Leptin Increases Adult Hippocampal Neurogenesis in Vivo and in Vitro J. Biol. Chem., June 27, 2008; 283(26): 18238 - 18247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kvajo, H. McKellar, P. A. Arguello, L. J. Drew, H. Moore, A. B. MacDermott, M. Karayiorgou, and J. A. Gogos A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition PNAS, May 13, 2008; 105(19): 7076 - 7081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Denis-Donini, A. Dellarole, P. Crociara, M. T. Francese, V. Bortolotto, G. Quadrato, P. L. Canonico, M. Orsetti, P. Ghi, M. Memo, et al. Impaired Adult Neurogenesis Associated with Short-Term Memory Defects in NF-{kappa}B p50-Deficient Mice J. Neurosci., April 9, 2008; 28(15): 3911 - 3919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kaslin, J. Ganz, and M. Brand Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain Phil Trans R Soc B, January 12, 2008; 363(1489): 101 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Lagace, M. C. Whitman, M. A. Noonan, J. L. Ables, N. A. DeCarolis, A. A. Arguello, M. H. Donovan, S. J. Fischer, L. A. Farnbauch, R. D. Beech, et al. Dynamic Contribution of Nestin-Expressing Stem Cells to Adult Neurogenesis J. Neurosci., November 14, 2007; 27(46): 12623 - 12629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ninkovic, T. Mori, and M. Gotz Distinct Modes of Neuron Addition in Adult Mouse Neurogenesis J. Neurosci., October 3, 2007; 27(40): 10906 - 10911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bruel-Jungerman, S. Davis, and S. Laroche Brain Plasticity Mechanisms and Memory: A Party of Four Neuroscientist, October 1, 2007; 13(5): 492 - 505. [Abstract] [PDF]
|
|
|
|
|
|
S. Jessberger, C. Zhao, N. Toni, G. D. Clemenson Jr, Y. Li, and F. H. Gage Seizure-Associated, Aberrant Neurogenesis in Adult Rats Characterized with Retrovirus-Mediated Cell Labeling J. Neurosci., August 29, 2007; 27(35): 9400 - 9407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Verret, J. L. Jankowsky, G. M. Xu, D. R. Borchelt, and C. Rampon Alzheimer's-Type Amyloidosis in Transgenic Mice Impairs Survival of Newborn Neurons Derived from Adult Hippocampal Neurogenesis J. Neurosci., June 20, 2007; 27(25): 6771 - 6780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sasaki, K. Kitagawa, E. Omura-Matsuoka, K. Todo, Y. Terasaki, S. Sugiura, J. Hatazawa, Y. Yagita, and M. Hori The Phosphodiesterase Inhibitor Rolipram Promotes Survival of Newborn Hippocampal Neurons After Ischemia Stroke, May 1, 2007; 38(5): 1597 - 1605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tashiro, H. Makino, and F. H. Gage Experience-Specific Functional Modification of the Dentate Gyrus through Adult Neurogenesis: A Critical Period during an Immature Stage J. Neurosci., March 21, 2007; 27(12): 3252 - 3259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Becker, V. Lavie, and B. Solomon Stimulation of endogenous neurogenesis by anti-EFRH immunization in a transgenic mouse model of Alzheimer's disease PNAS, January 30, 2007; 104(5): 1691 - 1696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. C. Piatti, M. S. Esposito, and A. F. Schinder The Timing of Neuronal Development in Adult Hippocampal Neurogenesis Neuroscientist, December 1, 2006; 12(6): 463 - 468. [Abstract] [PDF]
|
|
|
|
|
|
U Shivraj Sohur, J. G Emsley, B. D Mitchell, and J. D Macklis Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells Phil Trans R Soc B, September 29, 2006; 361(1473): 1477 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Synowitz, R. Glass, K. Farber, D. Markovic, G. Kronenberg, K. Herrmann, J. Schnermann, C. Nolte, N. van Rooijen, J. Kiwit, et al. A1 Adenosine Receptors in Microglia Control Glioblastoma-Host Interaction. Cancer Res., September 1, 2006; 66(17): 8550 - 8557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Buckwalter, M. Yamane, B. S. Coleman, B. K. Ormerod, J. T. Chin, T. Palmer, and T. Wyss-Coray Chronically Increased Transforming Growth Factor-{beta}1 Strongly Inhibits Hippocampal Neurogenesis in Aged Mice Am. J. Pathol., July 1, 2006; 169(1): 154 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Sun, A. Y. Shih, H. C. Johannssen, H. Erb, P. Li, and T. H. Murphy Two-photon Imaging of Glutathione Levels in Intact Brain Indicates Enhanced Redox Buffering in Developing Neurons and Cells at the Cerebrospinal Fluid and Blood-Brain Interface J. Biol. Chem., June 23, 2006; 281(25): 17420 - 17431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bruel-Jungerman, S. Davis, C. Rampon, and S. Laroche Long-term potentiation enhances neurogenesis in the adult dentate gyrus. J. Neurosci., May 31, 2006; 26(22): 5888 - 5893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hajszan and N. J. MacLusky Neurologic links between epilepsy and depression in women: Is hippocampal neuroplasticity the key? Neurology, March 28, 2006; 66(66_suppl_3): S13 - S22. [Abstract] [Full Text]
|
|
|
|
|
|
S. Jacobs, D. C. Lie, K. L. DeCicco, Y. Shi, L. M. DeLuca, F. H. Gage, and R. M. Evans Retinoic acid is required early during adult neurogenesis in the dentate gyrus PNAS, March 7, 2006; 103(10): 3902 - 3907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bick-Sander, B. Steiner, S. A. Wolf, H. Babu, and G. Kempermann Running in pregnancy transiently increases postnatal hippocampal neurogenesis in the offspring PNAS, March 7, 2006; 103(10): 3852 - 3857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Pozniak and S. J. Pleasure A Tale of Two Signals: Wnt and Hedgehog in Dentate Neurogenesis Sci. Signal., January 24, 2006; 2006(319): pe5 - pe5. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Kempermann, E. J. Chesler, L. Lu, R. W. Williams, and F. H. Gage Natural variation and genetic covariance in adult hippocampal neurogenesis PNAS, January 17, 2006; 103(3): 780 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Luzzati, S. De Marchis, A. Fasolo, and P. Peretto Neurogenesis in the Caudate Nucleus of the Adult Rabbit J. Neurosci., January 11, 2006; 26(2): 609 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zhao, E. M. Teng, R. G. Summers Jr, G.-l. Ming, and F. H. Gage Distinct Morphological Stages of Dentate Granule Neuron Maturation in the Adult Mouse Hippocampus J. Neurosci., January 4, 2006; 26(1): 3 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Bonaguidi, T. McGuire, M. Hu, L. Kan, J. Samanta, and J. A. Kessler LIF and BMP signaling generate separate and discrete types of GFAP-expressing cells Development, December 15, 2005; 132(24): 5503 - 5514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Esposito, V. C. Piatti, D. A. Laplagne, N. A. Morgenstern, C. C. Ferrari, F. J. Pitossi, and A. F. Schinder Neuronal Differentiation in the Adult Hippocampus Recapitulates Embryonic Development J. Neurosci., November 2, 2005; 25(44): 10074 - 10086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Maekawa, N. Takashima, Y. Arai, T. Nomura, K. Inokuchi, S. Yuasa, and N. Osumi Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis Genes Cells, October 1, 2005; 10(10): 1001 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Lombardino, X.-C. Li, M. Hertel, and F. Nottebohm Replaceable neurons and neurodegenerative disease share depressed UCHL1 levels PNAS, May 31, 2005; 102(22): 8036 - 8041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Abrous, M. Koehl, and M. Le Moal Adult Neurogenesis: From Precursors to Network and Physiology Physiol Rev, April 1, 2005; 85(2): 523 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Glass, M. Synowitz, G. Kronenberg, J.-H. Walzlein, D. S. Markovic, L.-P. Wang, D. Gast, J. Kiwit, G. Kempermann, and H. Kettenmann Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival J. Neurosci., March 9, 2005; 25(10): 2637 - 2646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nixon and F. T. Crews Temporally Specific Burst in Cell Proliferation Increases Hippocampal Neurogenesis in Protracted Abstinence from Alcohol J. Neurosci., October 27, 2004; 24(43): 9714 - 9722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Consiglio, A. Gritti, D. Dolcetta, A. Follenzi, C. Bordignon, F. H. Gage, A. L. Vescovi, and L. Naldini From the Cover: Robust in vivo gene transfer into adult mammalian neural stem cells by lentiviral vectors PNAS, October 12, 2004; 101(41): 14835 - 14840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Kramer, L. Bherer, S. J. Colcombe, W. Dong, and W. T. Greenough Environmental Influences on Cognitive and Brain Plasticity During Aging J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2004; 59(9): M940 - M957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Leuner, S. Mendolia-Loffredo, Y. Kozorovitskiy, D. Samburg, E. Gould, and T. J. Shors Learning Enhances the Survival of New Neurons beyond the Time when the Hippocampus Is Required for Memory J. Neurosci., August 25, 2004; 24(34): 7477 - 7481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-C. Wu, F. Chawla, D. Games, R. E. Rydel, S. Freedman, D. Schenk, W. G. Young, J. H. Morrison, and F. E. Bloom Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: Digital morphometric analyses PNAS, May 4, 2004; 101(18): 7141 - 7146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Lein, X. Zhao, and F. H. Gage Defining a Molecular Atlas of the Hippocampus Using DNA Microarrays and High-Throughput In Situ Hybridization J. Neurosci., April 14, 2004; 24(15): 3879 - 3889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fukuda, F. Kato, Y. Tozuka, M. Yamaguchi, Y. Miyamoto, and T. Hisatsune Two Distinct Subpopulations of Nestin-Positive Cells in Adult Mouse Dentate Gyrus J. Neurosci., October 15, 2003; 23(28): 9357 - 9366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ehninger and G. Kempermann Regional Effects of Wheel Running and Environmental Enrichment on Cell Genesis and Microglia Proliferation in the Adult Murine Neocortex Cereb Cortex, August 1, 2003; 13(8): 845 - 851. [Abstract] [Full Text] [PDF]
|
|
