The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Microglial numbers attain adult levels after undergoing a rapid decrease in cell number in the third postnatal week
Open accessAbstract
During postnatal development, microglia, CNS resident innate immune cells, are essential for synaptic pruning, neuronal apoptosis and remodeling. During this period microglia undergo morphological and phenotypic transformations; however, little is known about how microglial number and density is regulated during postnatal CNS development. We found that after an initial increase during the first 14 postnatal days, microglial numbers in mouse brain began declining in the third postnatal week and were reduced by 50% by 6weeks of age; these "adult" levels were maintained until at least 9months of age. Microglial CD11b levels increased, whereas CD45 and ER-MP58 declined between P10 and adulthood, consistent with a maturing microglial phenotype. Our data indicate that both increased microglial apoptosis and a decreased proliferative capacity contribute to the developmental reduction in microglial numbers. We found no correlation between developmental reductions in microglial numbers and brain mRNA levels of Cd200, Cx3Cl1, M-Csf or Il-34. We tested the ability of M-Csf-overexpression, a key growth factor promoting microglial proliferation and survival, to prevent microglial loss in the third postnatal week. Mice overexpressing M-Csf in astrocytes had higher numbers of microglia at all ages tested. However, the developmental decline in microglial numbers still occurred, suggesting that chronically elevated M-CSF is unable to overcome the developmental decrease in microglial numbers. Whereas the identity of the factor(s) regulating microglial number and density during development remains to be determined, it is likely that microglia respond to a "maturation" signal since the reduction in microglial numbers coincides with CNS maturation.
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“Microglia in the first two postnatal weeks are highly proliferative (Nikodemova et al., 2015).”
From Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing (2019) · cites this paper as Nikodemova et al., 2015
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Cites
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Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
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“Contrary to the developing brain, microglia in the healthy adult CNS have low mitotic activity (Harry and Kraft, 2012) and are characterized by a ramified morphology, with highly motile processes that constantly survey their microenvironment (Nimmerjahn et al., 2005).”
BackgroundFate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175 · cited 1×
“Contrary to neurons and glia that originate from the neuroectoderm, microglial cells are derived from mesodermal tissue originating in the yolk sac, and they populate the CNS during embryogenesis (Ginhoux et al., 2010; Schulz et al., 2012).”
BackgroundSynaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244 · cited 3×
“However, it is not yet clear whether the increased expression of these factors plays any role in the developmental regulation of microglial numbers, although mice lacking Cx3Cr1 (the receptor for CX3CL1), have slightly reduced microglial numbers between postnatal days 8 and 28 (Paolicelli et al., 2011).”
BackgroundMicroglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · cited 1×
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BackgroundATP mediates rapid microglial response to local brain injury in vivo
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BackgroundMutation of the mouse klotho gene leads to a syndrome resembling ageing
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“…(Paolicelli et al., 2011; Schafer et al., 2012; Tremblay et al., 2010; Wake et al., 2009); whereas in the adult CNS, microglia are involved in neuroplasticity, maintaining homeostasis and surveillance (Davalos et al., 2005; Kettenmann et al., 2011; Nimmerjahn et al., 2005; Parkhurst et al., 2013).”
BackgroundMicroglia promote learning-dependent synapse formation through brain-derived neurotrophic factor
Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W.-B. (2013) · Cell · doi:10.1016/j.cell.2013.11.030 · Cited by 2,599 · cited 2×
“…(Paolicelli et al., 2011; Schafer et al., 2012; Tremblay et al., 2010; Wake et al., 2009); whereas in the adult CNS, microglia are involved in neuroplasticity, maintaining homeostasis and surveillance (Davalos et al., 2005; Kettenmann et al., 2011; Nimmerjahn et al., 2005; Parkhurst et al., 2013).”
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Li, Q., Cheng, Z., Zhou, L., Darmanis, S., Neff, N. F., Okamoto, J., Gulati, G., Bennett, M. L., Sun, L. O., Clarke, L. E., et al. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.006 · Cited by 1,129
Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain
Askew, K., Li, K., Olmos-Alonso, A., Garcia-Moreno, F., Liang, Y., Richardson, P., Tipton, T., Chapman, M. A., Riecken, K., Beccari, S., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.041 · Cited by 726
“…invasive methods have revealed microglia to be highly dynamic in their interaction with the microenvironment, responding to inflammatory signals (Nimmerjahn et al., 2005; Davalos et al., 2005) and interacting with neuronal circuits at the synaptic level (Tremblay et al., 2010;Wake et al., 2009).”
BackgroundTay, T. L., Savage, J. C., Hui, C. W., Bisht, K., & Tremblay, M. (2017) · The Journal of Physiology · doi:10.1113/jp272134 · Cited by 562
“Interestingly the decline in microglial numbers after the third postnatal week was not mitigated by upregulating brain Csf-1 levels (Nikodemova et al. 2015), indicating the existence of alternative microglial responses to unknown developmental signals that drive the apoptosis of a population of microglial cells during…”
BackgroundInfluentialMicroglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function
Lenz, K. M., & Nelson, L. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00698 · Cited by 517
Elmore, M. R. P., Hohsfield, L. A., Kramár, E. A., Soreq, L., Lee, R. J., Pham, S. T., Najafi, A. R., Spangenberg, E. E., Wood, M. A., West, B. L., et al. (2018) · Aging Cell · doi:10.1111/acel.12832 · Cited by 380
Metadata
- Authors
- Nikodemova, M., Kimyon, R. S., De, I., Small, A. L., Collier, L. S., & Watters, J. J.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Watters, Jyoti J.
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 278
- Pages
- 280-288
- ISSN
- 0165-5728 (ISSN-L)
- PMC
- PMC4297717
- OpenAlex
- W1974031039
- Cited by
- 192
- References
- 56
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 12 · 2023: 20 · 2022: 16 · 2021: 31 · 2020: 24 · 2019: 17 · 2018: 11 · 2017: 11 · 2016: 11 · 2015: 4
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (NS049033, HL111598)
- Goldhirsh Foundation
- UW Madison Graduate School
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, postnatal brain development, microglial apoptosis, microglial proliferation, macrophage colony-stimulating factor, microglial maturation, CD11b, CD45, CD200, fractalkine, IL-34, microglial phenotype
- MeSH terms
- Aging, Animals, Animals, Newborn, Brain, Female, Flow Cytometry, Male, Mice, Inbred ICR, Cytokines, Apoptosis, Microglia, CD11b Antigen, Cell Proliferation, Mice
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