The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Microglia Shape Adult Hippocampal Neurogenesis through Apoptosis-Coupled Phagocytosis
Open accessAbstract
In the adult hippocampus, neuroprogenitor cells in the subgranular zone (SGZ) of the dentate gyrus give rise to newborn neuroblasts. However, only a small subset of these cells integrates into the hippocampal circuitry as mature neurons at the end of a 4 week period. Here, we show that the majority of the newborn cells undergo death by apoptosis in the first 1 to 4 days of their life, during the transition from amplifying neuroprogenitors to neuroblasts. These apoptotic newborn cells are rapidly cleared out through phagocytosis by unchallenged microglia present in the adult SGZ niche. Phagocytosis by the microglia is efficient and undeterred by increased age or inflammatory challenge. Our results suggest that the main critical period of newborn cell survival occurs within a few days of birth and reveal a new role for microglia in maintaining the homeostasis of the baseline neurogenic cascade.
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“microglia are considered as active regulators of adult neurogenesis,19”
From Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression (2022) · cites this paper as [19]
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“If this occurs during aging or disease states, axonal degeneration boosts microglial phagocytosis [328].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [328]
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“Under homeostatic conditions, microglia contribute to the regulation of numerous physiological functions, including neurogenesis,66,67 angiogenesis,68 maintaining BBB integrity,69 synaptic pruning and remodeling,70,71 synaptic transmission,72–74 myelin health,75,76 as well as phagocytosis and removal of apoptotic neurons and cellular debris.67,77,78”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [67]
In the citing paper
“Microglia contribute to neurogenesis in two ways: through phagocytosis of excessive newborn cells and by promoting neurogenesis through the secretion of cytokines.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [105]
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Cites
Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
Nicholson, D. W., Ali, A., Thornberry, N. A., Vaillancourt, J. P., Ding, C. K., Gallant, M., Gareau, Y., Griffin, P. R., Labelle, M., Lazebnik, Y. A., et al. (1995) · Nature · doi:10.1038/376037a0 · Cited by 3,980
ATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913
Kuhn, H., Dickinson-Anson, H., & Gage, F. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-06-02027.1996 · Cited by 3,139
Inflammatory Blockade Restores Adult Hippocampal Neurogenesis
Monje, M. L., Toda, H., & Palmer, T. D. (2003) · Science · doi:10.1126/science.1088417 · Cited by 2,426
Local self-renewal can sustain CNS microglia maintenance and function throughout adult life
Ajami, B., Bennett, J. L., Krieger, C., Tetzlaff, W., & Rossi, F. M. V. (2007) · Nature Neuroscience · doi:10.1038/nn2014 · Cited by 1,643
A blast from the past: clearance of apoptotic cells regulates immune responses
Savill, J., Dransfield, I., Gregory, C. D., & Haslett, C. (2002) · Nature reviews. Immunology · doi:10.1038/nri957 · Cited by 1,574
Inflammation is detrimental for neurogenesis in adult brain
Ekdahl, C. T., Claasen, J.-H., Bonde, S., Kokaia, Z., & Lindvall, O. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2234031100 · Cited by 1,559
Milestones of neuronal development in the adult hippocampus
Kempermann, G., Jessberger, S., Steiner, B., & Kronenberg, G. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.05.013 · Cited by 1,460
Cell death and control of cell survival in the oligodendrocyte lineage
Barres, B. A., Hart, I. K., Coles, H. S. R., Burne, J. F., Voyvodic, J. T., Richardson, W. D., & Raff, M. C. (1992) · Cell · doi:10.1016/0092-8674(92)90531-g · Cited by 1,345
Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus
Zhao, C., Teng, E. M., Summers, R. G., Ming, G.-L., & Gage, F. H. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3648-05.2006 · Cited by 1,257
Ziv, Y., Ron, N., Butovsky, O., Landa, G., Sudai, E., Greenberg, N., Cohen, H., Kipnis, J., & Schwartz, M. (2006) · Nature Neuroscience · doi:10.1038/nn1629 · Cited by 1,209
Debris clearance by microglia: an essential link between degeneration and regeneration
Neumann, H., Kotter, M. R., & Franklin, R. J. M. (2008) · Brain · doi:10.1093/brain/awn109 · Cited by 1,111
Butovsky, O., Ziv, Y., Schwartz, A., Landa, G., Talpalar, A. E., Pluchino, S., Martino, G., & Schwartz, M. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.10.006 · Cited by 923
Brain inflammation and adult neurogenesis: The dual role of microglia
Ekdahl, C. T., Kokaia, Z., & Lindvall, O. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2008.06.052 · Cited by 801
Microglia Promote the Death of Developing Purkinje Cells
Marı́n-Teva, J. L., Dusart, I., Colin, C., Gervais, A., van Rooijen, N., & Mallat, M. (2004) · Neuron · doi:10.1016/s0896-6273(04)00069-8 · Cited by 757
Neural stem and progenitor cells in nestin‐GFP transgenic mice
Mignone, J., Kukekov, V. G., Chiang, A., Steindler, D. A., & Enikolopov, G. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.10964 · Cited by 707
Self-citationMicroglia derived from aging mice exhibit an altered inflammatory profile
Sierra, A., Gottfried‐Blackmore, A. C., McEwen, B. S., & Bulloch, K. (2007) · Glia · doi:10.1002/glia.20468 · Cited by 688
Self-citationMaturation and Death of Adult-Born Olfactory Bulb Granule Neurons: Role of Olfaction
Petreanu, L., & Álvarez-Buylla, A. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-14-06106.2002 · Cited by 680
Sasmono, R. T., Oceandy, D., Pollard, J. W., Tong, W., Pavli, P., Wainwright, B. J., Ostrowski, M. C., Himes, S. R., & Hume, D. A. (2003) · Blood · doi:10.1182/blood-2002-02-0569 · Cited by 662
NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus
Tashiro, A., Sandler, V. M., Toni, N., Zhao, C., & Gage, F. H. (2006) · Nature · doi:10.1038/nature05028 · Cited by 640
Kronenberg, G., Reuter, K., Steiner, B., Brandt, M. D., Jessberger, S., Yamaguchi, M., & Kempermann, G. (2003) · Journal of Comparative Neurology · doi:10.1002/cne.10945 · Cited by 640 · cited 5×
“Based on published data of BrdU decay (Kempermann et al., 2004; Kronenberg et al., 2003; Mandyam et al., 2007), we hypothesized that newborn cells undergo apoptosis mostly during an early critical period and that the apoptotic debris is removed from the SGZ neurogenic niche by microglia.”
BackgroundResultInfluentialFluoxetine targets early progenitor cells in the adult brain
Encinas, J. M., Vaahtokari, A., & Enikolopov, G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601992103 · Cited by 637
Self-citationShort‐term and long‐term survival of new neurons in the rat dentate gyrus
Dayer, A. G., Ford, A. A., Cleaver, K. M., Yassaee, M., & Cameron, H. A. (2003) · Journal of Comparative Neurology · doi:10.1002/cne.10675 · Cited by 628
Biebl, M., Cooper, C., Winkler, J., & Kuhn, H. G. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01368-9 · Cited by 523
Dynamic Contribution of Nestin-Expressing Stem Cells to Adult Neurogenesis
Lagace, D. C., Whitman, M. C., Noonan, M. A., Ables, J. L., DeCarolis, N. A., Arguello, A. A., Donovan, M. H., Fischer, S. J., Farnbauch, L. A., Beech, R. D., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3812-07.2007 · Cited by 502
Live Astrocytes Visualized by Green Fluorescent Protein in Transgenic Mice
Zhuo, L., Sun, B., Zhang, C.-L., Fine, A., Chiu, S. Y., & Messing, A. (1997) · Developmental Biology · doi:10.1006/dbio.1997.8601 · Cited by 364
Apoptosis and Its Relation to the Cell Cycle in the Developing Cerebral Cortex
Thomaidou, D., Mione, M., Cavanagh, J. F. R., & Parnavelas, J. G. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-03-01075.1997 · Cited by 362
Recognition and phagocytosis of cells undergoing apoptosis
Savill, J. (1997) · British Medical Bulletin · doi:10.1093/oxfordjournals.bmb.a011626 · Cited by 331
Battista, D., Ferrari, C. C., Gage, F. H., & Pitossi, F. J. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04539.x · Cited by 306
Yang, F., Sun, X., Beech, W. K., Teter, B., Wu, S. S. H., Sigel, J. J., Vinters, H. V., Frautschy, S. A., & Cole, G. M. (1998) · Europe PMC (PubMed Central) · Cited by 245
Cell death in early neural development: beyond the neurotrophic theory
de la Rosa, E. J., & de Pablo, F. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01628-3 · Cited by 221
A Transgenic Marker for Newly Born Granule Cells in Dentate Gyrus
Overstreet‐Wadiche, L., Hentges, S. T., Bumaschny, V. F., de Souza, F. S. J., Smart, J. L., Santangelo, A. M., Low, M. J., Westbrook, G. L., & Rubinstein, M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5173-03.2004 · Cited by 207
Self-citationMandyam, C. D., Harburg, G. C., & Eisch, A. J. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.12.064 · Cited by 206
Sun, W., Winseck, A. K., Vinsant, S. L., Park, O., Kim, H., & Oppenheim, R. W. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1436-04.2004 · Cited by 203
Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice
Hayes, N. L., & Nowakowski, R. S. (2002) · Developmental Brain Research · doi:10.1016/s0165-3806(01)00324-8 · Cited by 201
The role of N ‐methyl‐ D ‐asparate receptors in neurogenesis
Nácher, J., & McEwen, B. S. (2006) · Hippocampus · doi:10.1002/hipo.20160 · Cited by 189
Identifying and Quantitating Neural Stem and Progenitor Cells in the Adult Brain
Encinas, J. M., & Enikolopov, G. (2008) · Methods in cell biology · doi:10.1016/s0091-679x(08)85011-x · Cited by 183
Self-citationKuhn, H. G., Biebl, M., Wilhelm, D., Li, M., Friedlander, R. M., & Winkler, J. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04377.x · Cited by 173
Glutamate and astrocytes—Key players in human mesial temporal lobe epilepsy?
Eid, T., Williamson, A., Lee, T.-S. W., Petroff, O. A. C., & de Lanerolle, N. C. (2008) · Epilepsia · doi:10.1111/j.1528-1167.2008.01492.x · Cited by 165
Activity‐dependent Extrinsic Regulation of Adult Olfactory Bulb and Hippocampal Neurogenesis
Ma, D. K., Kim, W. R., Ming, G., & Song, H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04373.x · Cited by 146
Diverse microglial motility behaviors during clearance of dead cells in hippocampal slices
Petersen, M. A., & Dailey, M. E. (2004) · Glia · doi:10.1002/glia.10362 · Cited by 139
Phagocytosis in the developing CNS: more than clearing the corpses
Mallat, M., Marín‐Teva, J. L., & Chéret, C. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.01.006 · Cited by 133
Ekdahl, C. T., Mohapel, P., Elmér, E., & Lindvall, O. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01713.x · Cited by 106
Weise, J., Engelhorn, T., Dörfler, A., Aker, S., Bähr, M., & Hufnagel, A. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.10.025 · Cited by 78
Control of Apoptosis by Asymmetric Cell Division
Hatzold, J., & Conradt, B. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060084 · Cited by 76
Kettenmann, H. (2007) · Nature · doi:10.1038/nature05713 · Cited by 73
Olah, M., Ping, G., Haas, A. H. D., Brouwer, N., Meerlo, P., van der Zee, E. A., Biber, K. P. H., & Boddeke, H. W. G. M. (2008) · Glia · doi:10.1002/glia.20828 · Cited by 66
Ekdahl, C. T., Zhu, C., Bonde, S., Bahr, B. A., Blomgren, K., & Lindvall, O. (2003) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.08.022 · Cited by 53
Ekdahl, C. T., Mohapel, P., Weber, E., Bahr, B. A., Blomgren, K., & Lindvall, O. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02202.x · Cited by 39
Aloisi, F. (2004) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195152227.003.0022 · Cited by 5
Mattson, M. (1999) · doi:10.1002/(sici)1097-4547(19991001)58:1
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Metadata
- Authors
- Sierra, A., Encinas, J. M., Deudero, J. J. P., Chancey, J. H., Enikolopov, G., Overstreet-Wadiche, L. S., Tsirka, S. E., & Maletic-Savatic, M.
- Affiliations
- Baylor College of Medicine (US)
- University of Alabama at Birmingham (US)
- Cold Spring Harbor Laboratory (US)
- Stony Brook University (US)
- Corresponding author
- Sierra, Amanda
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 7
- Issue
- 4
- Pages
- 483-495
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4008496
- OpenAlex
- W2160779535
- Cited by
- 1,622
- References
- 51
- Citations by year
- 2026: 73 · 2025: 103 · 2024: 128 · 2023: 109 · 2022: 137 · 2021: 151 · 2020: 142 · 2019: 120 · 2018: 97 · 2017: 102 · 2016: 99 · 2015: 94 · 2014: 89 · 2013: 79 · 2012: 64
- FWCI
- 17.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- Teva Pharmaceutical Industries
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS042168, K08NS044276, R21NS053875, R21NS05875-1, R01NS064025, K08NS0044276)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD024064)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- adult hippocampal neurogenesis, microglia, phagocytosis, apoptosis, newborn neurons, neural progenitor cells, subgranular zone, dentate gyrus, neuronal survival
- MeSH terms
- Animals, Hippocampus, Mice, Transgenic, Phagocytosis, Apoptosis, Mice, Neurogenesis, Neural Stem Cells
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