Microglia Shape Adult Hippocampal Neurogenesis through Apoptosis-Coupled Phagocytosis
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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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During aging or disease states, axonal degeneration boosts microglial phagocytosis.
“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]
The Results section on aging reports that microglial phagocytic efficiency in the hippocampal neurogenic niche remains constant across the ages studied; the Discussion also describes that efficiency as preserved during acute inflammation. Neither passage addresses whether axonal degeneration boosts phagocytosis during aging or disease (searched: axonal degeneration, degenerating axons). No page numbers were available in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measuredUnder homeostatic conditions, microglia contribute to the regulation of numerous physiological functions, including neurogenesis, angiogenesis, maintaining BBB integrity, synaptic pruning and remodeling, synaptic transmission, myelin health, as well as phagocytosis and removal of apoptotic neurons and cellular debris.
“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]
Microglia contribute to neurogenesis through phagocytosis of excessive newborn cells and by promoting neurogenesis through cytokine secretion, and phagocytosis depends on MERTK.
“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]
Microglia are active regulators of adult neurogenesis.
“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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- 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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