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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Microglia are highly proliferative during the first two postnatal weeks.
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023 · see citing works
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827 · cited 3× · see citing works
“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× · see citing works
“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× · see citing works
“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× · see citing works
“In the developing brain, microglia are essential for synaptic pruning, developmental neuronal apoptosis and remodeling (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…”
BackgroundATP 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 · cited 3× · see citing works
“to pathogens, injury or pathological processes, microglia become activated, and they can proliferate andmigrate to the site of disturbance (Davalos et al., 2005; Kettenmann et al., 2011).”
BackgroundMutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547 · cited 1× · see citing works
“…(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× · see citing works
“…(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).”
BackgroundA Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Schulz, C., Perdiguero, E. G., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E. W., Pollard, J. W., et al. (2012) · Science · doi:10.1126/science.1219179 · Cited by 2,578 · cited 1× · see citing works
“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).”
BackgroundElmore, M. R. P., Najafi, A. R., Koike, M. A., Dagher, N. N., Spangenberg, E. E., Rice, R. A., Kitazawa, M., Matusow, B., Nguyen, H., West, B. L., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.040 · Cited by 1,968 · see citing works
Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S., & Nabekura, J. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4363-08.2009 · Cited by 1,619 · cited 2× · see citing works
“In the developing brain, microglia are essential for synaptic pruning, developmental neuronal apoptosis and remodeling (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…”
BackgroundMicroglial interactions with synapses are modulated by visual experience
Tremblay, M.-È., Lowery, R. L., & Majewska, A. K. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000527 · Cited by 1,542 · cited 2× · see citing works
“…brain, microglia are essential for synaptic pruning, developmental neuronal apoptosis and remodeling (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…”
BackgroundMicroglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways
Kierdorf, K., Erny, D., Goldmann, T., Sander, V., Schulz, C., Perdiguero, E. G., Wieghofer, P., Heinrich, A., Riemke, P., Hölscher, C., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3318 · Cited by 1,457 · cited 1× · see citing works
“Recently, Kierdorf et al. (2013) identified CD45+ c-kitlo CX3CR1− cells in the yolk sac asmicroglial precursors that mature into CD45+ c-kit− CX3CR1+ cells that proliferate and differentiate into microglia in a Pu.1- and Irf8-dependent manner.”
BackgroundMicroglial cell origin and phenotypes in health and disease
Saijo, K., & Glass, C. K. (2011) · Nature Reviews Immunology · doi:10.1038/nri3086 · Cited by 1,100 · cited 1× · see citing works
“In the adult CNS, microglia are long-lived and have a very slow turn-over rate (Lawson et al., 1992; Saijo and Glass, 2011), and our data also support this observation.”
ResultWang, Y., Szretter, K. J., Vermi, W., Gilfillan, S., Rossini, C., Cella, M., Barrow, A. D., Diamond, M. S., & Colonna, M. (2012) · Nature Immunology · doi:10.1038/ni.2360 · Cited by 1,011 · cited 3× · see citing works
“To assess the potential regulatory mechanisms controlling developmental changes in microglial number, we evaluated brain expression levels of M-Csf and Il-34, key growth factors necessary for microglial proliferation and survival (Wang et al., 2012; Wegiel et al., 1998).”
BackgroundMethodThe Role of Microglia in the Healthy Brain: Figure 1.
Tremblay, M.-È., Stevens, B., Sierra, A., Wake, H., Bessis, A., & Nimmerjahn, A. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4158-11.2011 · Cited by 992 · cited 1× · see citing works
“Emerging studies suggest that microglia also play active roles in the healthy CNS (Tremblay et al., 2011).”
BackgroundMicroglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain
Alliot, F., Godin, I., & Pessac, B. (1999) · Developmental Brain Research · doi:10.1016/s0165-3806(99)00113-3 · Cited by 884 · cited 1× · see citing works
“Although microglia colonize the CNS during embryogenesis before the blood–brain-barrier closes, they retain high mitotic activity during the first two postnatal weeks, resulting in an increased number of these cells in the developing brain (Alliot et al., 1999; Zusso et al., 2012).”
BackgroundTurnover of resident microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., & Gordon, S. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90500-2 · Cited by 709 · see citing works
Sedgwick, J. D., Schwender, S., Imrich, H., Dörries, R., Butcher, G. W., & ter Meulen, V. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7438 · Cited by 691 · cited 1× · see citing works
“In the adult brain, microglia typically express CD11b and low levels of CD45 (Nikodemova and Watters, 2012), distinguishing them frommacrophages that are characterized by high CD11b and CD45 expression (Sedgwick et al., 1991).”
BackgroundSex differences in microglial colonization of the developing rat brain
Schwarz, J. M., Sholar, P. W., & Bilbo, S. D. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07630.x · Cited by 672 · cited 5× · see citing works
“Decreased Cd200 expression in the adult CNS is in linewith previous reports (Schwarz et al., 2012).”
BackgroundResultInfluentialErblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., & Pollard, J. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026317 · Cited by 649 · cited 1× · see citing works
“Mice lacking the receptor for macrophage-colony stimulating factor (CSF1R) are severely depleted of microglia (Erblich et al., 2011), suggesting that this receptor is essential for microglial development.”
BackgroundChapter 11 DAPI Staining of Fixed Cells for High-Resolution Flow Cytometry of Nuclear DNA
Otto, F. (1990) · Methods in cell biology · doi:10.1016/s0091-679x(08)60516-6 · Cited by 563 · cited 1× · see citing works
“3A) as has been reported previously (Otto, 1990).”
Lee, S., Varvel, N. H., Konerth, M. E., Xu, G., Cardona, A. E., Ransohoff, R. M., & Lamb, B. T. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100265 · Cited by 539 · cited 3× · see citing works
“, 2007; Eyo and Wu, 2013), that regulate microglial proliferation and/or survival in vivo and in vitro (Boehme et al., 2000; Chitnis et al., 2007; Deckert et al., 2006; Lee et al., 2010; Liu et al., 2013, 2014; Tang et al., 2014).”
BackgroundWakselman, S., Béchade, C., Roumier, A., Bernard, D., Triller, A., & Bessis, A. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1006-08.2008 · Cited by 351 · cited 1× · see citing works
“CD11b and CD45 are cell surface proteins important for immune cell function, and expression levels of thesemarkers can be used to distinguish different subsets of immune cells including microglia (CD11b/CD45) and macrophages (CD11b/CD45) (Penninger et al., 2001; Schafer et al., 2012; Wakselman et al., 2008).”
BackgroundNandi, S., Gökhan, Ş., Dai, X.-M., Wei, S., Enikolopov, G., Lin, H., Mehler, M. F., & Stanley, E. R. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.03.026 · Cited by 342 · cited 1× · see citing works
“Both M-CSF and IL-34, ligands for the CSF1R, are highly expressed in the CNS (Berezovskaya et al., 1995; Nandi et al., 2012; Wang et al., 2012).”
BackgroundCrain, J. M., Nikodémová, M., & Watters, J. J. (2013) · Journal of Neuroscience Research · doi:10.1002/jnr.23242 · Cited by 334 · cited 2× · see citing works
“genes in postnatalmicroglia, although they did not acquire the typicalM1 phenotype (Crain et al., 2013).”
BackgroundMicroglial cell population dynamics in the injured adult central nervous system
Ladeby, R., Wirenfeldt, M., Garcia-Ovejero, D., Fenger, C., Dissing-Olesen, L., Dalmau, I., & Finsen, B. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.12.009 · Cited by 334 · cited 1× · see citing works
“Indeed, many CNS disorders are characterized by a several fold in microglial cell numbers (Ladeby et al., 2005; Nikodemova et al., 2014).”
BackgroundCD45: new jobs for an old acquaintance
Penninger, J. M., Irie-Sasaki, J., Sasaki, T., & Oliveira-dos-Santos, A. (2001) · Nature Immunology · doi:10.1038/87687 · Cited by 305 · cited 1× · see citing works
“CD11b and CD45 are cell surface proteins important for immune cell function, and expression levels of thesemarkers can be used to distinguish different subsets of immune cells including microglia (CD11b/CD45) and macrophages (CD11b/CD45) (Penninger et al., 2001; Schafer et al., 2012; Wakselman et al., 2008).”
BackgroundMicroglia in the developing brain: a potential target with lifetime effects
Harry, G. J., & Kraft, A. D. (2012) · NeuroToxicology · doi:10.1016/j.neuro.2012.01.012 · Cited by 250 · cited 4× · see citing works
“The total number ofmicroglia in brain parenchyma increases during the first two postnatal weeks as has been previously reported (Dalmau et al., 2003; Harry and Kraft, 2012), reaching a peak around 14 days of age.”
BackgroundInfluentialImamoto, K., & Leblond, C. P. (1978) · The Journal of Comparative Neurology · doi:10.1002/cne.901800109 · Cited by 234 · cited 1× · see citing works
“We found that in the adult brain, only a small percentage of CD11b cells (around 4%) are in the G2/M phase as assayed by DNA content, and less than 2%expressKi67, a nuclear protein associated with proliferation, consistent with previous reports using autoradiography (Imamoto and Leblond, 1978).”
ResultBidirectional Microglia‐Neuron Communication in the Healthy Brain
Eyo, U. B., & Wu, L. (2013) · Neural Plasticity · doi:10.1155/2013/456857 · Cited by 203 · see citing works
Tang, Z., Gan, Y. X., Liu, Q., Yin, J., Liu, Q., Shi, J., & Shi, F. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-26 · Cited by 192 · cited 3× · see citing works
“, 2007; Eyo and Wu, 2013), that regulate microglial proliferation and/or survival in vivo and in vitro (Boehme et al., 2000; Chitnis et al., 2007; Deckert et al., 2006; Lee et al., 2010; Liu et al., 2013, 2014; Tang et al., 2014).”
BackgroundThe Chemokine Fractalkine Inhibits Fas-Mediated Cell Death of Brain Microglia
Boehme, S. A., Lio, F. M., Maciejewski-Lenoir, D., Bacon, K. B., & Conlon, P. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.1.397 · Cited by 192 · cited 3× · see citing works
“, 2007; Eyo and Wu, 2013), that regulate microglial proliferation and/or survival in vivo and in vitro (Boehme et al., 2000; Chitnis et al., 2007; Deckert et al., 2006; Lee et al., 2010; Liu et al., 2013, 2014; Tang et al., 2014).”
BackgroundDynamics of microglia in the developing rat brain
Dalmau, I., Vela, J. M., González, B., Finsen, B. R., & Castellano, B. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10572 · Cited by 167 · cited 1× · see citing works
“The total number ofmicroglia in brain parenchyma increases during the first two postnatal weeks as has been previously reported (Dalmau et al., 2003; Harry and Kraft, 2012), reaching a peak around 14 days of age.”
BackgroundEfficient isolation of live microglia with preserved phenotypes from adult mouse brain
Nikodémová, M., & Watters, J. J. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-147 · Cited by 165 · see citing works
Synapse elimination in the developing cerebellum
Hashimoto, K., & Kano, M. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1405-2 · Cited by 154 · cited 1× · see citing works
“Because the majority of synaptic pruning, neuronal circuit refinement and myelination occurs during the first three postnatal weeks of mouse brain development (Hashimoto and Kano, 2013; Verma et al., 2005), microglia play a vital role in all of these processes, and the reduction in microglial number coincides with CNS…”
BackgroundZusso, M., Methot, L., Lo, R., Greenhalgh, A. D., David, S., & Stifani, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6182-11.2012 · Cited by 154 · cited 1× · see citing works
“Although microglia colonize the CNS during embryogenesis before the blood–brain-barrier closes, they retain high mitotic activity during the first two postnatal weeks, resulting in an increased number of these cells in the developing brain (Alliot et al., 1999; Zusso et al., 2012).”
BackgroundChitnis, T., Imitola, J., Wang, Y., Elyaman, W., Chawla, P., Sharuk, M., Raddassi, K., Bronson, R. T., & Khoury, S. J. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060677 · Cited by 142 · cited 4× · see citing works
“, 2007; Eyo and Wu, 2013), that regulate microglial proliferation and/or survival in vivo and in vitro (Boehme et al., 2000; Chitnis et al., 2007; Deckert et al., 2006; Lee et al., 2010; Liu et al., 2013, 2014; Tang et al., 2014).”
BackgroundInfluentialExpression of P2 nucleotide receptors varies with age and sex in murine brain microglia
Crain, J. M., Nikodémová, M., & Watters, J. J. (2009) · Journal of Neuroinflammation · doi:10.1186/1742-2094-6-24 · Cited by 122 · see citing works
Węgiel, J., Wı́sniewski, H. M., Dziewiątkowski, J., Tarnawski, M. J., Kozielski, R., Trenkner, E., & Wiktor-Jędrzejczak, W. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00618-0 · Cited by 120 · see citing works
Wu, C., Wen, C. Y., Shieh, J., & Ling, E. (1992) · Europe PMC (PubMed Central) · Cited by 94 · see citing works
Berezovskaya, O. L., Maysinger, D., & FEDOROFF, S. (1995) · International Journal of Developmental Neuroscience · doi:10.1016/0736-5748(95)00013-7 · Cited by 93 · see citing works
Novel zinc-based fixative for high quality DNA, RNA and protein analysis
Lykidis, D., Noorden, S. V., Armstrong, A., Spencer‐Dene, B., Li, J., Zhuang, Z., & Stamp, G. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm433 · Cited by 89 · see citing works
Deckert, M., Sedgwick, J. D., Fischer, E., & Schlüter, D. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0062-z · Cited by 82 · cited 3× · see citing works
“, 2007; Eyo and Wu, 2013), that regulate microglial proliferation and/or survival in vivo and in vitro (Boehme et al., 2000; Chitnis et al., 2007; Deckert et al., 2006; Lee et al., 2010; Liu et al., 2013, 2014; Tang et al., 2014).”
BackgroundCSF1 overexpression has pleiotropic effects on microglia in vivo
De, I., Nikodémová, M., Steffen, M. D., Sokn, E., Maklakova, V. I., Watters, J. J., & Collier, L. S. (2014) · Glia · doi:10.1002/glia.22717 · Cited by 79 · cited 6× · see citing works
“5 times more microglia in the adult CNS (P42) compared to littermate controls (De et al., 2014); (Fig.”
BackgroundMethodInfluentialVerma, R., Mori, S., Shen, D. G., Yarowsky, P., Zhang, J., & Davatzikos, C. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407828102 · Cited by 77 · cited 1× · see citing works
“Because the majority of synaptic pruning, neuronal circuit refinement and myelination occurs during the first three postnatal weeks of mouse brain development (Hashimoto and Kano, 2013; Verma et al., 2005), microglia play a vital role in all of these processes, and the reduction in microglial number coincides with CNS…”
BackgroundNikodémová, M., Small, A. L., Smith, S. M. C., Mitchell, G. S., & Watters, J. J. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.11.009 · Cited by 74 · cited 2× · see citing works
“Indeed, many CNS disorders are characterized by a several fold in microglial cell numbers (Ladeby et al., 2005; Nikodemova et al., 2014).”
BackgroundChan, J. M. K., Leenen, P. J. M., Bertoncello, I., Nishikawa, S., & Hamilton, J. A. (1998) · Blood · doi:10.1182/blood.v92.4.1423 · Cited by 69 · see citing works
Nikodémová, M., & Watters, J. J. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.006 · Cited by 62 · cited 1× · see citing works
“RNA isolation and qRT-PCR were performed as we described in detail previously (Crain et al., 2009; Nikodemova and Watters, 2011).”
MethodKondo, Y., & Duncan, I. D. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22096 · Cited by 60 · cited 1× · see citing works
“M-CSF-deficient op/op mice and IL-34-deficient mice have significantly decreased numbers of microglia in the CNS (Kondo and Duncan, 2009;Wang et al., 2012).”
BackgroundInterplay between human microglia and neural stem/progenitor cells in an allogeneic co‐culture model
Liu, J., Hjorth, E., Zhu, M., Calzarossa, C., Samuelsson, E., Schultzberg, M., & Åkesson, E. (2013) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12123 · Cited by 48 · see citing works
Smith, S. M. C., Kimyon, R. S., & Watters, J. J. (2014) · ASN NEURO · doi:10.1042/an20130050 · Cited by 30 · cited 1× · see citing works
“All appropriate compensation and fluorescence minus one (FMO) controls were performed and utilized in the analysis, as previously described (Smith et al., 2014).”
MethodJensen, U. B., Owens, D. M., Pedersen, S. L., & Christensen, R. (2010) · Cytometry Part A · doi:10.1002/cyto.a.20914 · Cited by 26 · cited 1× · see citing works
“7) and glycerol (1:1), as previously described (Jensen et al., 2010; Lykidis et al., 2007), until further analysis.”
MethodCX 3 CR 1 RNA i inhibits hypoxia‐induced microglia activation via p38 MAPK / PKC pathway
Liu, Y., Zhao, T., Yang, Z., & Li, Q. (2014) · International Journal of Experimental Pathology · doi:10.1111/iep.12065 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
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 · see citing works
“…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 · see citing works
“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 491 · see citing works
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 · see citing works
Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System
Chiţu, V., Gökhan, Ş., Nandi, S., Mehler, M. F., & Stanley, E. R. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.03.005 · Cited by 354 · see citing works
Hu, Y., Fryatt, G. L., Ghorbani, M., Obst, J., Menassa, D. A., Martin-Estebane, M., Muntslag, T. A. O., Olmos-Alonso, A., Guerrero-Carrasco, M., Thomas, D., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109228 · Cited by 298 · see citing works
Microglia in depression: current perspectives
Jia, X., Gao, Z., & Hu, H. (2020) · Science China Life Sciences · doi:10.1007/s11427-020-1815-6 · Cited by 283 · see citing works
“Microglia rapidly expand at perinatal and postnatal stages and fully colonize the brain by the end of the second week (Bennett et al., 2016; Nikodemova et al., 2015).”
BackgroundMicroglia in CNS development: Shaping the brain for the future
Mosser, C., Baptista, S., Arnoux, I., & Audinat, É. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.01.002 · Cited by 268 · see citing works
“…heterogeneous until the end of the first postnatal week (Arnoux et al., 2013) and microglia density reaches a peak during the second postnatal week before decreasing and stabilizing at adult levels only by the end of the first postnatal month (Nikodemova et al., 2015; Paolicelli et al., 2011).”
Microglia-neuron crosstalk: Signaling mechanism and control of synaptic transmission
Marinelli, S., Basilico, B., Marrone, M. C., & Ragozzino, D. (2019) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.05.017 · Cited by 233 · see citing works
Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease
Czapski, G. A., & Strosznajder, J. B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111677 · Cited by 194 · see citing works
“The analysis of rodent development demonstrated that in the postnatal period the number of microglial cells in the brain initially increases, and then their population begins declining, due to developmental apoptosis and decreased proliferation [23].”
BackgroundCommunicating systems in the body: how microbiota and microglia cooperate
Erny, D., de Angelis, A. L. H., & Prinz, M. (2016) · Immunology · doi:10.1111/imm.12645 · Cited by 190 · see citing works
Microglial/Macrophage polarization and function in brain injury and repair after stroke
Lyu, J., Xie, D., Bhatia, T. N., Leak, R. K., Hu, X., & Jiang, X. (2021) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13620 · Cited by 171 · see citing works
Microglia plasticity during health and disease: An immunological perspective
Shemer, A., Erny, D., Jung, S., & Prinz, M. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.003 · Cited by 168 · see citing works
A Developmental Analysis of Juxtavascular Microglia Dynamics and Interactions with the Vasculature
Mondo, E., Becker, S. C., Kautzman, A. G., Schifferer, M., Baer, C. E., Chen, J., Huang, E. J., Simons, M., & Schafer, D. P. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.3006-19.2020 · Cited by 146 · see citing works
Developmental Cell Death in the Cerebral Cortex
Wong, F. K., & Marín, Ó. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100818-125204 · Cited by 128 · see citing works
“However, microglia numbers are dramatically reduced by approximately 50% between the third and sixth postnatal week (Nikodemova et al. 2015).”
BackgroundMicroglia-driven regulation of oligodendrocyte lineage cells, myelination, and remyelination
Miron, V. E. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ri1116-494r · Cited by 134 · see citing works
Nelson, L. H., & Lenz, K. M. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.09.006 · Cited by 120 · see citing works
Microglia: Brain cells on the move
Smolders, S., Kessels, S., Vangansewinkel, T., Rigo, J., Legendre, P., & Brône, B. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.04.001 · Cited by 114 · see citing works
Prata, J., Santos, S. G., Almeida, M. I., Coelho, R., & Barbosa, M. A. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0938-y · Cited by 115 · see citing works
Microglia: Lifelong patrolling immune cells of the brain
Eyo, U. B., & Wu, L. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.04.003 · Cited by 112 · see citing works
Nerve injury and neuropathic pain — A question of age
Fitzgerald, M., & McKelvey, R. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.07.013 · Cited by 109 · see citing works
The immune system as a novel regulator of sex differences in brain and behavioral development
Nelson, L. H., & Lenz, K. M. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23821 · Cited by 107 · see citing works
“Microglia subsequently undergo a cull that mirrors the overproduction and programmed loss of neurons in the developing brain (Nikodemova et al., 2015).”
BackgroundInfluentialMenassa, D. A., Muntslag, T. A. O., Martín‐Estebané, M., Barry-Carroll, L., Chapman, M. A., Adorján, I., Tyler, T., Turnbull, B., Rose-Zerilli, M. J. J., Nicoll, J. A. R., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2022.07.015 · Cited by 108 · see citing works
Savage, J. C., St‐Pierre, M., Carrier, M., Hajj, H. E., Novak, S. W., Sánchez, M. G., Cicchetti, F., & Tremblay, M. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01782-9 · Cited by 99 · see citing works
“This is in line with prior studies finding that microglial brain density decreases in mice from 3 to 6 weeks of age, at which point it stabilizes [59].”
ResultMicroglia in brain development and regeneration
Mehl, L. C., Manjally, A. V., Bouadi, O., Gibson, E. M., & Tay, T. L. (2022) · Development · doi:10.1242/dev.200425 · Cited by 103 · see citing works
New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective
Pósfai, B., Cserép, C., Orsolits, B., & Dénes, Á. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.04.046 · Cited by 98 · see citing works
Santos, S. E. D., Medeiros, M., Porfírio, J., Tavares, W. C., Pessôa, L. M., Grinberg, L. T., Leite, R. E. P., Ferretti‐Rebustini, R. E. D. L., Suemoto, C. K., Filho, W. J., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2339-19.2020 · Cited by 96 · see citing works
“In mice, total numbers of microglial cells were found to peak at 3weeks after birth and to decrease thereafter, showing similar densities at 1 and 9months of age (Nikodemova et al., 2015).”
BackgroundMicroglia: Driving critical periods and sexual differentiation of the brain
VanRyzin, J. W., Pickett, L. A., & McCarthy, M. M. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22569 · Cited by 93 · see citing works
“Once in the brain, these cells continue to migrate, proliferate, and mature throughout Developmental Neurobiology development, until microglia attain their adult phenotype by the end of the third postnatal week (Ajami et al., 2007; Swinnen et al., 2013; Elmore et al., 2014; Nikodemova et al., 2015).”
BackgroundArreola, M. A., Soni, N., Crapser, J. D., Hohsfield, L. A., Elmore, M. R. P., Matheos, D. P., Wood, M. A., Swarup, V., Mortazavi, A., & Green, K. N. (2021) · Science Advances · doi:10.1126/sciadv.abg1601 · Cited by 89 · see citing works
Microglia Diversity in Healthy and Diseased Brain: Insights from Single-Cell Omics
Ochocka, N., & Kaminska, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063027 · Cited by 91 · see citing works
“The density of microglia in the developing CNS is two times higher than in the adult CNS, and the time-regulated decline in microglia number involves increased apoptosis and reduced proliferation [26].”
BackgroundOligodendroglial α‐synucleinopathy‐driven neuroinflammation in multiple system atrophy
Hoffmann, A., Ettle, B., Battis, K., Reiprich, S., Schlachetzki, J. C. M., Masliah, E., Wegner, M., Kuhlmann, T., Riemenschneider, M. J., & Winkler, J. (2019) · Brain Pathology · doi:10.1111/bpa.12678 · Cited by 83 · see citing works
“Under physiological conditions, microglia proliferation peaks within the second postnatal week and declines afterward into a lower turnover rate including proliferation and apoptosis cycles (3, 59).”
BackgroundMicroglia and sexual differentiation of the developing brain: A focus on extrinsic factors
VanRyzin, J. W., Marquardt, A. E., Pickett, L. A., & McCarthy, M. M. (2019) · Glia · doi:10.1002/glia.23740 · Cited by 81 · see citing works
“…of the third postnatal week in the rodent—when much of early brain development is done—microglia will have tiled throughout the brain and attained their adult phenotype of highly ramified, surveillant cells (Davalos et al., 2005; Nikodemova et al., 2015; Nimmerjahn, Kirchhoff, & Helmchen, 2005).”
BackgroundVanRyzin, J. W., Yu, S. J., Perez‐Pouchoulen, M., & McCarthy, M. M. (2016) · eNeuro · doi:10.1523/eneuro.0297-16.2016 · Cited by 83 · see citing works
“2016 1–19 (Davalos et al., 2005; Nimmerjahn et al., 2005; Schwarz et al., 2012; Nikodemova et al., 2015).”
Microglia: origins, homeostasis, and roles in myelin repair
Lloyd, A. F., Davies, C. L., & Miron, V. E. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.001 · Cited by 83 · see citing works
Rossi, C., Cusimano, M., Zambito, M., Finardi, A., Capotondo, A., Garcia-Manteiga, J. M., Comi, G., Furlan, R., Martino, G., & Muzio, L. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0288-4 · Cited by 77 · see citing works
Anwar, S., & Rivest, S. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1738391 · Cited by 78 · see citing works
Bordeleau, M., Carrier, M., Luheshi, G. N., & Tremblay, M.-È. (2019) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.06.001 · Cited by 75 · see citing works
How microbiota shape microglial phenotypes and epigenetics
Erny, D., & Prinz, M. (2020) · Glia · doi:10.1002/glia.23822 · Cited by 77 · see citing works
Carroll, L., Braeutigam, S., Dawes, J. M., Krsnik, Ž., Kostović, I., Coutinho, E., Dewing, J. M., Horton, C. A., Gómez‐Nicola, D., & Menassa, D. A. (2020) · The Neuroscientist · doi:10.1177/1073858420921378 · Cited by 75 · see citing works
Deciphering sex differences in the immune system and depression
Rainville, J. R., Tsyglakova, M., & Hodes, G. E. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.12.004 · Cited by 69 · see citing works
Delbridge, A. R. D., Huh, D., Brickelmaier, M., Burns, J. C., Roberts, C., Challa, R., Raymond, N., Cullen, P., Carlile, T. M., Ennis, K. A., et al. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.592005 · Cited by 72 · see citing works
“, 2018), this microglia phenotype trajectory was also consistent with the known developmental changes that occur from the neonatal period to adulthood (Nikodemova et al., 2015; Matcovitch-Natan et al., 2016).”
Leung, G., Cool, T., Valencia, C. H., Worthington, A. K., Beaudin, A. E., & Forsberg, E. C. (2019) · Development · doi:10.1242/dev.176180 · Cited by 67 · see citing works
“…fits with recent reports of rapid changes in proliferation and apoptosis occurring postnatally in microglia (Askew D E V E LO P M E N T et al., 2017; Nikodemova et al., 2015), and suggests the possibility that IL7Rα contributes to proliferation or survival of microglia in the transition between…”
BackgroundTay, T. L., Carrier, M., & Tremblay, M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-9913-8_6 · Cited by 61 · see citing works
Nelson, L. H., Saulsbery, A. I., & Lenz, K. M. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.09.002 · Cited by 61 · see citing works
“Microglia sample their local microenvironment by extending and retracting their many processes (Nimmerjahn, 2005).”
The ins and outs of microglial cells in brain health and disease
Pallarés-Moratalla, C., & Bergers, G. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1305087 · Cited by 60 · see citing works
A story of birth and death: Insights into the formation and dynamics of the microglial population
Askew, K. E., & Gómez‐Nicola, D. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.03.009 · Cited by 55 · see citing works
Microglia as therapeutic target in central nervous system disorders
Fatoba, O., Itokazu, T., & Yamashita, T. (2020) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2020.07.004 · Cited by 56 · see citing works
The force awakens: insights into the origin and formation of microglia
Tay, T. L., Hagemeyer, N., & Prinz, M. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.04.003 · Cited by 57 · see citing works
Colony stimulating factors in the nervous system
Chiţu, V., Biundo, F., & Stanley, E. R. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101511 · Cited by 55 · see citing works
Regulation of microglia population dynamics throughout development, health, and disease
Hammond, B. P., Manek, R., Kerr, B. J., Macauley, M. S., & Plemel, J. R. (2021) · Glia · doi:10.1002/glia.24047 · Cited by 56 · see citing works
Bodnar, B. H., Zhang, Y., Liu, J., Lin, Y., Wang, P., Wei, Z., Saribas, S., Zhu, Y., Li, F., Wang, X., et al. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.682272 · Cited by 56 · see citing works
“One limit of this study is the small number ofmicroglia cells in MCO (around 7%), although it may represent the physiological development process (Lawson et al., 1992; Nikodemova et al., 2015; Bachiller et al., 2018).”
BackgroundBarry-Carroll, L., Greulich, P., Marshall, A. R., Riecken, K., Fehse, B., Askew, K. E., Li, K., Garaschuk, O., Menassa, D. A., & Gómez‐Nicola, D. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112425 · Cited by 52 · see citing works
Johnson, S. M., Randhawa, K. S., Epstein, J. J., Gustafson, E., Hocker, A. D., Huxtable, A. G., Baker, T. L., & Watters, J. J. (2017) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2017.11.007 · Cited by 51 · see citing works
“…including autism spectrum disorder (Squarzoni et al., 2014; Zhan et al., 2014), schizophrenia (Ma et al., 2013; Paolicelli et al., 2011), Fragile-X syndrome (Higashimori et al., 2013; Jacobs et al., 2010), depression (Nishiyama et al., 2002), and obsessive compulsive disorder (Zhan et al., 2014).”
BackgroundOntogeny of adult neural stem cells in the mammalian brain
Bond, A. M., Ming, G., & Song, H. (2020) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2020.11.002 · Cited by 48 · see citing works
Microglia in developing white matter and perinatal brain injury
McNamara, N. B., & Miron, V. E. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134539 · Cited by 45 · see citing works
The behavior and functions of embryonic microglia
Hattori, Y. (2021) · Anatomical Science International · doi:10.1007/s12565-021-00631-w · Cited by 46 · see citing works
Microglia in health and pain: impact of noxious early life events
Burke, N. N., Fan, C. Y., & Trang, T. (2016) · Experimental Physiology · doi:10.1113/ep085714 · Cited by 43 · see citing works
“2013), but as the nervous system matures, microglia transition to a ramified morphology (Schwarz et al. 2012; Nikodemova et al. 2015).”
BackgroundInfluentialImmune mechanisms of stress susceptibility and resilience: Lessons from animal models
Tsyglakova, M., McDaniel, D. K., & Hodes, G. E. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100771 · Cited by 44 · see citing works
Majcher‐Maślanka, I., Solarz, A., & Chocyk, A. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.10.033 · Cited by 42 · see citing works
The molecular determinants of microglial developmental dynamics
Barry-Carroll, L., & Gómez‐Nicola, D. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00813-1 · Cited by 45 · see citing works
“Like CSF1R, TREM2 has been implicated in driving the proliferative response of microglia in the adult brain in response to disease 15,122 and also relies on downstream signalling via the adaptor protein DAP12 (also known as TYROBP) and the AKT–MTOR and CEBPB pathways to induce proliferation 119,125…”
Go with your gut: microbiota meet microglia
Mosher, K. I., & Wyss‐Coray, T. (2015) · Nature Neuroscience · doi:10.1038/nn.4051 · Cited by 44 · see citing works
Microglia Phenotypes Following the Induction of Alcohol Dependence in Adolescent Rats
Peng, H., & Nixon, K. (2021) · Alcoholism: Clinical and Experimental Research · doi:10.1111/acer.14504 · Cited by 43 · see citing works
Hyperleptinemia as a contributing factor for the impairment of glucose intolerance in obesity
Pretz, D., Foll, C. L., Rizwan, M. Z., Lutz, T. A., & Tups, A. (2020) · The FASEB Journal · doi:10.1096/fj.202001147r · Cited by 42 · see citing works
Microglia heterogeneity in health and disease
Dadwal, S., & Heneka, M. T. (2023) · FEBS Open Bio · doi:10.1002/2211-5463.13735 · Cited by 44 · see citing works
“From Week 5 to 6, microglia density stabilizes [26].”
BackgroundA Comparative Biology of Microglia Across Species
Sharma, K. P., Bisht, K., & Eyo, U. B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.652748 · Cited by 39 · see citing works
“In addition to their complex morphology, microglia are the most morphologically dynamic cells of the vertebrate brain (Davalos et al., 2005; Nimmerjahn, 2012).”
BackgroundEyo, U. B., Miner, S. A., Weiner, J. A., & Dailey, M. E. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.11.009 · Cited by 39 · see citing works
“(2015), http://dx.doi.org/10.1016/j.bbi.201 development in the mouse (Nikodemova et al., 2015).”
InfluentialThe multifaceted roles of embryonic microglia in the developing brain
Hattori, Y. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.988952 · Cited by 39 · see citing works
The dual function of microglial polarization and its treatment targets in ischemic stroke
Mo, Y., Xu, W., Fu, K., Chen, H., Wen, J., Huang, Q., Guo, F., Mo, L., & Yan, J. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.921705 · Cited by 37 · see citing works
“A decrease in the rate of proliferation accompanied by an increase in apoptosis results in a decrease in the overall number of microglia, and mature microglia maintain their numbers in the CNS by self-renewal (23, 24).”
BackgroundStables, J., Green, E. K., Sehgal, A., Patkar, O. L., Keshvari, S., Taylor, I., Ashcroft, M. E., Grabert, K., Wollscheid-Lengeling, E., Szymkowiak, S., et al. (2022) · Development · doi:10.1242/dev.200237 · Cited by 38 · see citing works
de Soysa, Y., Therrien, M., Walker, A. C., & Stevens, B. (2022) · Seminars in Immunology · doi:10.1016/j.smim.2022.101651 · Cited by 33 · see citing works
Loss of microglial EED impairs synapse density, learning, and memory
Wang, Y.-Y., Deng, Y.-S., Dai, S.-K., Mi, T.-W., Li, R.-Y., Liu, P.-P., Liu, C., He, B.-D., He, X.-C., Du, H.-Z., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01576-w · Cited by 32 · see citing works
“The microglial population in the healthy brain is reduced by 50% and maintained in adulthood [45].”
BackgroundAlbertini, G., D’Andrea, I., Druart, M., Béchade, C., Nieves-Rivera, N., Etienne, F., Magueresse, C. L., Rebsam, A., Heck, N., Maroteaux, L., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02048-5 · Cited by 32 · see citing works
“During postnatal development, microglia also undergo a transition from amoeboid to rami fi ed [20, 21], in a sex-dependent manner [28].”
BackgroundOxytocin and microglia in the development of social behaviour
Gonzalez, A. M., & Hammock, E. A. D. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0059 · Cited by 32 · see citing works
Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brainPreprint
Zelco, A., Börjesson, V., de Kanter, J. K., Lebrero‐Fernández, C., Lauschke, V. M., Rocha‐Ferreira, E., Nilsson, G., Nair, S., Svedin, P., Bemark, M., et al. (2021) · Genes & Development · doi:10.1101/gad.348190.120 · Cited by 31 · see citing works
“(2019) In addition, subcluster 2 also showed enriched proliferative processes as seen previously for microglia in the first 2 wk of life (Nikodemova et al. 2015), and subcluster 13 seems to be involved in neurogenesis and nervous system development.”
BackgroundMicroglia in the Brain Tumor Microenvironment
Cole, A. P., Hoffmeyer, E., Chetty, S. L., Cruz, J. C., Hamrick, F. A., Youssef, O. A., Cheshier, S. H., & Mitra, S. S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-49270-0_11 · Cited by 30 · see citing works
A critical postnatal period of heightened vulnerability to lipopolysaccharide
Rourke, K. S., Mayer, C. A., & MacFarlane, P. M. (2016) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2016.06.003 · Cited by 28 · see citing works
Microglial regulation of satiety and cognition
Luca, S. N. D., Miller, A. A., Sominsky, L., & Spencer, S. J. (2020) · Journal of Neuroendocrinology · doi:10.1111/jne.12838 · Cited by 27 · see citing works
Establishment of tissue-resident immune populations in the fetus
Feyaerts, D., Urbschat, C., Gaudilliere, B. L., & Stelzer, I. A. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00931-x · Cited by 27 · see citing works
“From rodent studies, it is known that their numbers contract in postnatal week 3 and subsequently stabilize to adult levels after week 4 [145, 146].”
BackgroundOsborne, B. F., Turano, A., Caulfield, J. I., & Schwarz, J. M. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.10.044 · Cited by 27 · see citing works
Morphological evidence indicates a role for microglia in shaping the PCOS‐like brain
Sati, A., Prescott, M., Holland, S., Jasoni, C. L., Desroziers, E., & Campbell, R. E. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12999 · Cited by 26 · see citing works
Astrocytes and microglia in the coordination of CNS development and homeostasis
Lopez‐Ortiz, A. O., & Eyo, U. B. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.16006 · Cited by 29 · see citing works
“However, microglial numbers peak in the second week of post-natal development (Kim et al., 2015; Nikodemova et al., 2015) and are trimmed by the third week (Nikodemova et al., 2015; Paolicelli et al., 2011), and although astrocytes have not been documented to be instrumental in the reduction of…”
Riquier, A. J., & Sollars, S. I. (2019) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2019.100010 · Cited by 26 · see citing works
Modulatory effects of mesenchymal stem cells on microglia in ischemic stroke
Hao, L., Yang, Y., Xu, X., Guo, X., & QunLing, Z. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2022.1073958 · Cited by 25 · see citing works
“There are more microglia in the hippocampus and the olfactory bulb and fewer microglia in the fiber bundle (25).”
BackgroundLoewen, S. M., Chavesa, A. M., Murray, C. J., Traetta, M. E., Burns, S. E., Pekarik, K. H., & Tremblay, M. (2023) · Developmental Neuroscience · doi:10.1159/000530185 · Cited by 25 · see citing works
Nitric oxide signaling inhibits microglia proliferation by activation of protein kinase-G
Maksoud, M., Tellios, V., Xiang, Y., & Lu, W.-Y. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.11.005 · Cited by 23 · see citing works
First Encounters: Effects of the Microbiota on Neonatal Brain Development
Gars, A., Ronczkowski, N. M., Chassaing, B., Castillo‐Ruiz, A., & Forger, N. G. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.682505 · Cited by 24 · see citing works
Solarz, A., Majcher‐Maślanka, I., Kryst, J., & Chocyk, A. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.11.005 · Cited by 24 · see citing works
Developmental functions of microglia: Impact of psychosocial and physiological early life stress
Smail, M. A., & Lenz, K. M. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110084 · Cited by 22 · see citing works
“The hippocampus (HPC), cortex (CTX), and amygdala (AMY) are some of the first regions”
The Complementary Role of Morphology in Understanding Microglial Functional Heterogeneity
Godeanu, S., & Cătălin, B. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083811 · Cited by 21 · see citing works
“This balance can vary over time, with an increase in apoptosis and a decrease in proliferation being noted immediately postnatally [43].”
Sex- and Development-Dependent Responses of Rat Microglia to Pro- and Anti-inflammatory Stimulation
Lively, S. S., Wong, R., Lam, D., & Schlichter, L. C. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00433 · Cited by 20 · see citing works
“Increasingly, it is recognized that sex can profoundly influence both the susceptibility and response to disease (Ober et al., 2008; Regitz-Zagrosek, 2012).”
BackgroundSingle-cell RNA sequencing identifies hippocampal microglial dysregulation in diet-induced obesity
Henn, R. E., Guo, K., Elzinga, S. E., Noureldein, M. H., Mendelson, F. E., Hayes, J. M., Rigan, D. M., Savelieff, M. G., Hur, J., & Feldman, E. L. (2023) · iScience · doi:10.1016/j.isci.2023.106164 · Cited by 18 · see citing works
Microglia in pediatric brain tumors: The missing link to successful immunotherapy
du Chatinier, A., Velilla, I. Q., Meel, M. H., Hoving, E. W., Hulleman, E., & Metselaar, D. S. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101246 · Cited by 20 · see citing works
“5 8 However, the role of developmental microglia in pediatric brain tumors is not well understood, despite a noteworthy increase in interest in this topic.”
BackgroundLewen, A., Ta, T., Cesetti, T., Hollnagel, J., Papageorgiou, I. E., Chausse, B., & Kann, O. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24689 · Cited by 18 · see citing works
“2.7 | Recordings of local field potential and [K+]o For electrophysiological recordings, the intact Biopore™ membrane carrying slice cultures was inserted into the recording chamber (Kann et al., 2011; Papageorgiou et al., 2016).”
BackgroundMethodInfluentialClinical and experimental aspects of breathing modulation by inflammation
Peña‐Ortega, F. (2018) · Autonomic Neuroscience · doi:10.1016/j.autneu.2018.11.002 · Cited by 19 · see citing works
Boyle, B. R., Melli, S. E., Altreche, R. S., Padron, Z. M., Yousufzai, F. A. K., Kim, S., Vasquez, M. D., Carone, D. M., Carone, B. R., & Soto, I. (2020) · Development · doi:10.1242/dev.189019 · Cited by 18 · see citing works
“Interestingly, a reduced number of cerebellar granule cells and reductions in cerebellar lobule size at the end of postnatal development have been found in Npc1−/− mice (Nusca et al., 2014).”
BackgroundSkowronski, A. A., LeDuc, C. A., Foo, K. S., Goffer, Y., Burnett, L. C., Egli, D. M., & Leibel, R. L. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aax6629 · Cited by 18 · see citing works
Daura, E., Tegelberg, S., Hakala, P., Lehesjoki, A., & Joensuu, T. H. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1069122 · Cited by 15 · see citing works
“In wt cerebellum, the percentage of dividing microglia decreased from approximately 16% at P14 to 1% at P21 and at P30, in line with previous findings (Nikodemova et al., 2015).”
BackgroundResultThe Potential Impact of the Gut Microbiota on Neonatal Brain Development and Adverse Health Outcomes
Tzitiridou‐Chatzopoulou, M., Kountouras, J., & Ζουρνατζίδου, Γ. (2024) · Children · doi:10.3390/children11050552 · Cited by 16 · see citing works
“Additionally, these microglia experience alterations in their physical structure and gene expression [1].”
BackgroundRiquier, A. J., & Sollars, S. I. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.04.037 · Cited by 16 · see citing works
“…determine if the time course of microglia presence in the developing rat rNTS is similar to that observed in other brain areas (Alliot et al., 1999; Nikodemova et al., 2015), and to determine whether microglia density differences correspond to known periods of CT terminal field pruning (Sollars et…”
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
