Layer V cortical neurons require microglial support for survival during postnatal development
Abstract
Neurons require trophic support during neural circuit formation; however, how the cellular milieu contributes to neuronal survival remains unclear. We found that layer V cortical neurons require support from microglia for survival during postnatal development. Specifically, we found that microglia accumulated close to the subcerebral and callosal projection axons in the postnatal brain. Inactivation of microglia by minocycline treatment or transient ablation of microglia in CD11b-DTR transgenic mice led to increased apoptosis, specifically in layer V subcerebral and callosal projection neurons. CX3CR1 in microglia was required for the survival of layer V neurons. Microglia consistently promoted the survival of cortical neurons in vitro. In addition, we identified microglia-derived IGF1 as a trophic factor that maintained neuronal survival. Our results highlight a neuron-glia interaction that is indispensable for network formation during a specific period in the developing brain.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Another group showed that these microglia were the predominant source of Igf1 in the early postnatal brain, and Igf1 conditional knockout in microglia affected developing cortical neuron health at the same age.
“Another group showed that these microglia were the predominant source of Igf1 in the early postnatal brain, and Igf1 conditional knockout in microglia affected the health of developing cortical neurons at the same age (Ueno et al., 2013).”
From Complex cell-state changes revealed by single cell RNA sequencing of 76,149 microglia throughout the mouse lifespan and in the injured brain (2018) · cites this paper as Ueno et al., 2013
Igf1 is abundantly expressed by microglia during postnatal development, aging, or following brain injuries and plays a vital role in promoting neuronal survival.
“Igf1 is abundantly expressed by microglia during postnatal development, aging or following brain injuries and plays a vital role in promoting neuronal survival (59,63–66).”
From <i>Trem2</i> promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [63]
Cites
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 · see citing works
Fate 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 · see citing works
Neurotrophins: Roles in Neuronal Development and Function
Huang, E. J., & Reichardt, L. F. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.677 · Cited by 4,394 · see citing works
Synaptic 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 · see citing works
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · see citing works
Cellular Actions of the Insulin-Like Growth Factor Binding Proteins
Firth, S. M., & Baxter, R. C. (2002) · Endocrine Reviews · doi:10.1210/er.2001-0033 · Cited by 1,754 · see citing works
Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R., & Iredale, J. P. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522675 · Cited by 1,649 · 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 · see citing works
The P2Y12 receptor regulates microglial activation by extracellular nucleotides
Haynes, S. E., Hollopeter, G., Yang, G., Kurpius, D., Dailey, M. E., Gan, W.-B., & Julius, D. (2006) · Nature Neuroscience · doi:10.1038/nn1805 · Cited by 1,542 · see citing works
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · see citing works
Neuronal Subtype-Specific Genes that Control Corticospinal Motor Neuron Development In Vivo
Arlotta, P., Molyneaux, B. J., Chen, J., Inoue, J., Kominami, R., & Macklis, J. D. (2005) · Neuron · doi:10.1016/j.neuron.2004.12.036 · Cited by 1,157 · see citing works
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 · see citing works
Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia
Yrjänheikki, J., Keinänen, R., Pellikka, M., Hökfelt, T., & Koistinaho, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15769 · Cited by 1,006 · see citing works
Tikka, T., Fiebich, B. L., Goldsteins, G., Keinänen, R., & Koistinaho, J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-08-02580.2001 · Cited by 958 · see citing works
Microglia 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 · see citing works
Selective Ablation of Proliferating Microglial Cells Exacerbates Ischemic Injury in the Brain
Lalancette-Hébert, M., Gowing, G., Simard, A., Weng, Y. C., & Kriz, J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5360-06.2007 · Cited by 874 · see citing works
AXON RETRACTION AND DEGENERATION IN DEVELOPMENT AND DISEASE
Luo, L., & O’Leary, D. D. M. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135632 · Cited by 844 · see citing works
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 · see citing works
Satb2 Regulates Callosal Projection Neuron Identity in the Developing Cerebral Cortex
Alcamo, E. A., Chirivella, L., Dautzenberg, M., Dobreva, G., Fariñas, I., Grosschedl, R., & McConnell, S. K. (2008) · Neuron · doi:10.1016/j.neuron.2007.12.012 · Cited by 658 · see citing works
Beck, K. D., Powell-Braxtont, L., Widmer, H.-R., Valverde, J., & Hefti, F. (1995) · Neuron · doi:10.1016/0896-6273(95)90216-3 · Cited by 636 · see citing works
Brewer, G. J. (1995) · Journal of Neuroscience Research · doi:10.1002/jnr.490420510 · Cited by 546 · see citing works
Dittgen, T., Nimmerjahn, A., Komai, S., Licznerski, P., Waters, J., Margrie, T. W., Helmchen, F., Denk, W., Brecht, M., & Osten, P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407976101 · Cited by 485 · see citing works
Hematopoietic origin of pathological grooming in Hoxb8 mutant mice
Chen, S.-K., Tvrdik, P., Peden, E., Cho, S., Wu, S., Spangrude, G., & Capecchi, M. R. (2010) · Cell · doi:10.1016/j.cell.2010.03.055 · Cited by 450 · see citing works
The origin and cell lineage of microglia: new concepts
Chan, W. Y., Kohsaka, S., & Rezaie, P. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.11.002 · Cited by 400 · see citing works
Chemokines and Chemokine Receptors: Standing at the Crossroads of Immunobiology and Neurobiology
Ransohoff, R. M. (2009) · Immunity · doi:10.1016/j.immuni.2009.09.010 · Cited by 372 · see citing works
Microglia-Derived Nerve Growth Factor Causes Cell Death in the Developing Retina
Frade, J. M., & Barde, Y. (1998) · Neuron · doi:10.1016/s0896-6273(00)80432-8 · Cited by 341 · see citing works
IGF-I specifically enhances axon outgrowth of corticospinal motor neurons
Özdinler, P. H., & Macklis, J. D. (2006) · Nature Neuroscience · doi:10.1038/nn1789 · Cited by 341 · see citing works
O’Leary, D. D. M., & Terashima, T. (1988) · Neuron · doi:10.1016/0896-6273(88)90147-x · Cited by 304 · see citing works
Milligan, C. E., Cunningham, T. J., & Levitt, P. R. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903140112 · Cited by 252 · see citing works
Cailhier, J. F., Partolina, M., Vuthoori, S., Wu, S., Ko, K. A., Watson, S. J., Savill, J., Hughes, J., & Lang, R. A. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.4.2336 · Cited by 244 · see citing works
Activity-Dependent Development of Callosal Projections in the Somatosensory Cortex
Wang, C., Zhang, L., Zhou, Y., Zhou, J., Yang, X.-J., Duan, S., Xiong, Z., & Ding, Y. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3380-07.2007 · Cited by 214 · see citing works
Inhibition of cellular proliferation by peptide analogues of insulin-like growth factor 1.
Pietrzkowski, Z. J., Wernicke, D., Porcu, P., Jameson, B. A., & Baserga, R. (1992) · PubMed · Cited by 184 · see citing works
Endogenous microglia regulate development of embryonic cortical precursor cells
Antony, J. M., Paquin, A., Nutt, S. L., Kaplan, D. R., & Miller, F. D. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22533 · Cited by 157 · see citing works
Microglia and Macrophages in the Developing CNS
Streit, W. J. (2001) · NeuroToxicology · doi:10.1016/s0161-813x(01)00033-x · Cited by 134 · see citing works
Ueno, M., Hayano, Y., Nakagawa, H., & Yamashita, T. (2012) · Brain · doi:10.1093/brain/aws053 · Cited by 124 · see citing works
Self-citationActivated Microglia Inhibit Axonal Growth through RGMa
Kitayama, M., Ueno, M., Itakura, T., & Yamashita, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025234 · Cited by 116 · see citing works
Self-citationMolecular mechanisms of axon guidance in the developing corticospinal tract
Canty, A. J., & Murphy, M. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.02.001 · Cited by 106 · see citing works
Hristova, M., Cuthill, D., Zbarsky, V., Acosta‐Saltos, A., Wallace, A. S., Blight, K., Buckley, S. M. K., Peebles, D., Heuer, H., Waddington, S. N., et al. (2009) · Glia · doi:10.1002/glia.20896 · Cited by 105 · see citing works
Dugas, J. C., Mandemakers, W. J., Rogers, M., Ibrahim, A., Daneman, R., & Barres, B. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2010-08.2008 · Cited by 99 · see citing works
Akazawa, H., Komazaki, S., Shimomura, H., Terasaki, F., Zou, Y., Takano, H., Nagai, T., & Komuro, I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313084200 · Cited by 93 · see citing works
Catapano, L. A., Arnold, M. W., Perez, F. A., & Macklis, J. D. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-22-08863.2001 · Cited by 89 · see citing works
Valverde, F., López‐Mascaraque, L., Santacana, M., & Carlos, J. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-07-05014.1995 · Cited by 87 · see citing works
Engulfment of Axon Debris by Microglia Requires p38 MAPK Activity
Tanaka, T., Ueno, M., & Yamashita, T. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.005603 · Cited by 86 · see citing works
Self-citationMicroglia: its development and role as a neuropathology sensor
Ling, E., Ng, Y. K., Wu, C., & Kaur, C. (2001) · Progress in brain research · doi:10.1016/s0079-6123(01)32066-6 · Cited by 83 · see citing works
Postnatal growth of corticospinal axons in the spinal cord of developing mice
Gianino, S. M., Stein, S. A., Li, H., Lu, X., Biesiada, E., Ułas, J., & Xu, X. (1999) · Developmental Brain Research · doi:10.1016/s0165-3806(98)00168-0 · Cited by 78 · see citing works
Koester, S. E., & O’Leary, D. D. M. (1993) · Developmental Biology · doi:10.1006/dbio.1993.1281 · Cited by 74 · see citing works
del Río, P., Irmler, M., Arango‐González, B., Favor, J., Bobe, C., Bartsch, U., Vecino, E., Beckers, J., Hauck, S. M., & Ueffing, M. (2011) · Glia · doi:10.1002/glia.21155 · Cited by 74 · see citing works
Murase, S., & Hayashi, Y. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-24-10481.1998 · Cited by 31 · see citing works
Insulin-like growth factor binding protein-1-6 expression in activated microglia
Chesik, D., Glazenburg, K. L., Wilczak, N., Geeraedts, F., & Keyser, J. D. (2004) · Neuroreport · doi:10.1097/00001756-200404290-00020 · Cited by 20 · see citing works
Strategies for regenerating injured axons after spinal cord injury – insights from brain development
Yamashita, T. (2008) · Biologics · doi:10.2147/btt.s2715 · Cited by 13 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
CSF-1R inhibition alters macrophage polarization and blocks glioma progression
Pyonteck, S. M., Akkari, L., Schuhmacher, A. J., Bowman, R. L., Sevenich, L., Quail, D. F., Olson, O. C., Quick, M. L., Huse, J. T., Teijeiro, V., et al. (2013) · Nature Medicine · doi:10.1038/nm.3337 · Cited by 2,463 · see citing works
Hammond, T. R., Dufort, C., Dissing-Olesen, L., Giera, S., Young, A., Wysoker, A., Walker, A. J., Segel, M., Nemesh, J., Saunders, A., et al. (2018) · doi:10.1101/406140 · Cited by 2,225 · see citing works
Microglia and macrophages in brain homeostasis and disease
Li, Q., & Barres, B. A. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.125 · Cited by 1,999 · see citing works
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
Origin and functions of tissue macrophages
Epelman, S., Lavine, K. J., & Randolph, G. J. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.013 · Cited by 1,585 · see citing works
A polarizing question: do M1 and M2 microglia exist?
Ransohoff, R. M. (2016) · Nature Neuroscience · doi:10.1038/nn.4338 · Cited by 1,573 · see citing works
Microglia Biology: One Century of Evolving Concepts
Prinz, M., Jung, S., & Priller, J. (2019) · Cell · doi:10.1016/j.cell.2019.08.053 · Cited by 1,525 · see citing works
Microglia development and function
Nayak, D., Roth, T. L., & McGavern, D. B. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120240 · Cited by 1,154 · see citing works
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
Microglia-mediated neuroinflammation in neurodegenerative diseases
Subhramanyam, C. S., Wang, C., Hu, Q., & Dheen, S. T. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.004 · Cited by 875 · see citing works
The Semantics of Microglia Activation: Neuroinflammation, Homeostasis, and Stress
Woodburn, S. C., Bollinger, J. L., & Wohleb, E. S. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02309-6 · Cited by 783 · see citing works
Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
Thion, M. S., Low, D., Silvin, A., Chen, J., Grisel, P., Schulte-Schrepping, J., Blecher, R., Ulas, T., Squarzoni, P., Hoeffel, G., et al. (2018) · Cell · doi:10.1016/j.cell.2017.11.042 · Cited by 779 · see citing works
Microglia monitor and protect neuronal function through specialized somatic purinergic junctions
Cserép, C., Pósfai, B., Lénárt, N., Fekete, R., László, Z. I., Lele, Z., Orsolits, B., Molnár, G., Heindl, S., Schwarcz, A. D., et al. (2020) · Science · doi:10.1126/science.aax6752 · Cited by 684 · see citing works
Microglia Modulate Wiring of the Embryonic Forebrain
Squarzoni, P., Oller, G., Hoeffel, G., Pont‐Lezica, L., Rostaing, P., Low, D., Bessis, A., Ginhoux, F., & Garel, S. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.042 · Cited by 655 · see citing works
Cell-to-cell Communication by Extracellular Vesicles: Focus on Microglia
Paolicelli, R. C., Bergamini, G., & Rajendran, L. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.04.003 · Cited by 599 · see citing works
Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation
Prinz, M., Masuda, T., Wheeler, M. A., & Quintana, F. J. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-110159 · Cited by 584 · see citing works
Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease
Singh, D. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02565-0 · Cited by 569 · see citing works
Tay, 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
Hagemeyer, N., Hanft, K.-M., Akriditou, M.-A., Unger, N., Park, E. S., Stanley, E. R., Staszewski, O., Dimou, L., & Prinz, M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1747-1 · Cited by 558 · see citing works
New insights on the role of microglia in synaptic pruning in health and disease
Hong, S., Dissing-Olesen, L., & Stevens, B. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.12.004 · Cited by 557 · see citing works
Physiology and diseases of tissue-resident macrophages
Lazarov, T., Juarez-Carreño, S., Cox, N., & Geissmann, F. (2023) · Nature · doi:10.1038/s41586-023-06002-x · Cited by 540 · see citing works
A novel microglial subset plays a key role in myelinogenesis in developing brain
Wlodarczyk, A., Holtman, I. R., Krueger, M., Yogev, N., Bruttger, J., Khorooshi, R., Benmamar‐Badel, A., de Boer‐Bergsma, J. J., Martin, N. A., Karram, K., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201696056 · Cited by 535 · see citing works
Sublime Microglia: Expanding Roles for the Guardians of the CNS
Salter, M. W., & Beggs, S. (2014) · Cell · doi:10.1016/j.cell.2014.06.008 · Cited by 531 · see citing works
The Indispensable Roles of Microglia and Astrocytes during Brain Development
Reemst, K., Noctor, S. C., Lucassen, P. J., & Hol, E. M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00566 · Cited by 516 · see citing works
Eyo, U. B., Peng, J., Swiatkowski, P., Mukherjee, A., Bispo, A., & Wu, L.-J. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0416-14.2014 · Cited by 509 · see citing works
Yu, X., Liu, H., Hamel, K. A., Morvan, M. G., Yu, S. W., Leff, J., Guan, Z., Braz, J. M., & Basbaum, A. I. (2020) · Nature Communications · doi:10.1038/s41467-019-13839-2 · Cited by 508 · see citing works
Microglia 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
Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects
Kim, H.-J., Cho, M.-H., Shim, W. H., Kim, J. K., Jeon, E.-Y., Kim, D.-H., & Yoon, S.-Y. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.103 · Cited by 475 · see citing works
Microbiome–microglia connections via the gut–brain axis
Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180794 · Cited by 471 · see citing works
“In addition to dictating neuronal density, microglia supply a steady stream of neurotrophic factors (such as nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], and insulin-like growth factor 1 [IGF-1]) that promote neuronal survival and differentiation of neural progenitors (Gomes et al., 2013; Ueno…”
BackgroundBidirectional Microglia–Neuron Communication in Health and Disease
Szepesi, Z., Manouchehrian, O., Bachiller, S., & Deierborg, T. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00323 · Cited by 459 · see citing works
Astrocytes and microglia: In sickness and in health
Vainchtein, I. D., & Molofsky, A. V. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.01.003 · Cited by 450 · see citing works
TREM2, microglia, and neurodegenerative diseases
Yeh, F. L., Hansen, D. V., & Sheng, M. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.008 · Cited by 440 · see citing works
Microglia and early brain development: An intimate journey
Thion, M. S., Ginhoux, F., & Garel, S. (2018) · Science · doi:10.1126/science.aat0474 · Cited by 440 · see citing works
Estrogens, Neuroinflammation, and Neurodegeneration
Villa, A., Vegeto, E., Poletti, A., & Maggi, A. (2016) · Endocrine Reviews · doi:10.1210/er.2016-1007 · Cited by 423 · see citing works
Microglia morphophysiological diversity and its implications for the CNS
Vidal-Itriago, A., Radford, R. A. W., Aramideh, J. A., Maurel, C., Scherer, N. M., Don, E. K., Lee, A., Chung, R. S., Graeber, M. B., & Morsch, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.997786 · Cited by 412 · see citing works
Directed differentiation of human pluripotent stem cells to microglia
Douvaras, P., Sun, B., Wang, M., Kruglikov, I., Lallos, G., Zimmer, M., Terrenoire, C., Zhang, B., Gandy, S., Schadt, E., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.04.023 · Cited by 381 · see citing works
The pro-remyelination properties of microglia in the central nervous system
Lloyd, A. F., & Miron, V. E. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0184-2 · Cited by 381 · 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
Purinergic receptor P2RY12-dependent microglial closure of the injured blood–brain barrier
Lou, N., Takano, T., Pei, Y., Xavier, A. L., Goldman, S. A., & Nedergaard, M. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520398113 · Cited by 364 · see citing works
Microglia: Architects of the Developing Nervous System
Frost, J. L., & Schafer, D. P. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.02.006 · Cited by 362 · see citing works
Microglia Function in Central Nervous System Development and Plasticity
Schafer, D. P., & Stevens, B. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020545 · Cited by 353 · see citing works
Microglia in the Retina: Roles in Development, Maturity, and Disease
Silverman, S. M., & Wong, W. T. (2018) · Annual Review of Vision Science · doi:10.1146/annurev-vision-091517-034425 · Cited by 351 · see citing works
Microglia Phenotypes in Aging and Neurodegenerative Diseases
Wendimu, M. Y., & Hooks, S. B. (2022) · Cells · doi:10.3390/cells11132091 · Cited by 336 · see citing works
Microglia and Inflammatory Responses in Diabetic Retinopathy
Kinuthia, U. M., Wolf, A., & Langmann, T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.564077 · Cited by 326 · see citing works
The effects of microglia-associated neuroinflammation on Alzheimer’s disease
Wang, C., Zong, S., Cui, X., Wang, X., Wu, S., Wang, L., Liu, Y., & Lu, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1117172 · Cited by 318 · see citing works
Novel Hexb-based tools for studying microglia in the CNS
Masuda, T., Amann, L., Sankowski, R., Staszewski, O., Lenz, M., d´Errico, P., Snaidero, N., Costa Jordão, M. J., Böttcher, C., Kierdorf, K., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0707-4 · Cited by 317 · see citing works
Fractalkine regulation of microglial physiology and consequences on the brain and behavior
Paolicelli, R. C., Bisht, K., & Tremblay, M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00129 · Cited by 314 · see citing works
Microglia in Health and Disease
Ransohoff, R. M., & Khoury, J. E. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020560 · Cited by 303 · see citing works
Microglial TREM2/DAP12 signaling: a double-edged sword in neural diseases
Konishi, H., & Kiyama, H. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00206 · Cited by 300 · see citing works
Microglia–Neuron Communication in Epilepsy
Eyo, U. B., Murugan, M., & Wu, L. (2016) · Glia · doi:10.1002/glia.23006 · Cited by 290 · see citing works
Inflammation and the neural diathesis-stress hypothesis of schizophrenia: a reconceptualization
Howes, O. D., & McCutcheon, R. (2017) · Translational Psychiatry · doi:10.1038/tp.2016.278 · Cited by 288 · see citing works
Kierdorf, K., & Prinz, M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90602 · Cited by 283 · see citing works
The Contribution of Microglia to Neuroinflammation in Parkinson’s Disease
Badanjak, K., Fixemer, S., Smajić, S., Skupin, A., & Grünewald, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094676 · Cited by 281 · see citing works
Arcuri, C., Mecca, C., Bianchi, R., Giambanco, I., & Donato, R. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00191 · Cited by 279 · see citing works
Switching of the Microglial Activation Phenotype Is a Possible Treatment for Depression Disorder
Zhang, L., Zhang, J., & You, Z. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00306 · Cited by 279 · see citing works
VanRyzin, J. W., Marquardt, A. E., Argue, K. J., Vecchiarelli, H. A., Ashton, S. E., Arambula, S. E., Hill, M. N., & McCarthy, M. M. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.006 · Cited by 272 · see citing works
Resident and Monocyte-Derived Macrophages in Cardiovascular Disease
Honold, L., & Nahrendorf, M. (2018) · Circulation Research · doi:10.1161/circresaha.117.311071 · Cited by 272 · see citing works
The human microglial HMC3 cell line: where do we stand? A systematic literature review
Russo, C. D., Cappoli, N., Coletta, I., Mezzogori, D., Paciello, F., Pozzoli, G., Navarra, P., & Battaglia, A. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1288-0 · Cited by 271 · see citing works
Microglia 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
DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways
Nardone, S., Sharan Sams, D., Reuveni, E., Getselter, D., Oron, O., Karpuj, M., & Elliott, E. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.70 · Cited by 266 · see citing works
Tmem119-EGFP and Tmem119-CreERT2 Transgenic Mice for Labeling and Manipulating Microglia
Kaiser, T., & Feng, G. (2019) · eneuro · doi:10.1523/eneuro.0448-18.2019 · Cited by 259 · see citing works
To Kill a Microglia: A Case for CSF1R Inhibitors
Green, K. N., Crapser, J. D., & Hohsfield, L. A. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.07.001 · Cited by 259 · see citing works
Aging Microglia—Phenotypes, Functions and Implications for Age-Related Neurodegenerative Diseases
Spittau, B. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00194 · Cited by 258 · see citing works
Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions
Cserép, C., Pósfai, B., & Dénes, Á. (2021) · Neuron · doi:10.1016/j.neuron.2020.11.007 · Cited by 256 · see citing works
Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders
Zengeler, K. E., & Lukens, J. R. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-020-00487-7 · Cited by 254 · see citing works
Goshi, N., Morgan, R. K., Lein, P. J., & Şeker, E. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01819-z · Cited by 248 · see citing works
Neuroinflammation: Ways in Which the Immune System Affects the Brain
Ransohoff, R. M., Schafer, D. P., Vincent, A. C., Blachère, N. E., & Bar‐Or, A. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0385-3 · Cited by 245 · see citing works
Wang, X., Zhao, L., Zhang, J., Fariss, R. N., Ma, W., Kretschmer, F., Wang, M., Qian, H., Badea, T. C., Diamond, J. S., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3575-15.2016 · Cited by 242 · see citing works
Paolicelli, R. C., & Ferretti, M. T. (2017) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2017.00009 · Cited by 235 · see citing works
Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS
Illés, P., Rubini, P., Ulrich, H., Zhao, Y., & Tang, Y. (2020) · Cells · doi:10.3390/cells9051108 · Cited by 235 · see citing works
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
Glial Cells Shape Pathology and Repair After Spinal Cord Injury
Gaudet, A. D., & Fonken, L. K. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0630-7 · Cited by 232 · see citing works
Immune modulation by MANF promotes tissue repair and regenerative success in the retina
Neves, J., Zhu, J., Sousa‐Victor, P., Konjikusic, M. J., Riley, R. R., Chew, S., Qi, Y., Jasper, H., & Lamba, D. A. (2016) · Science · doi:10.1126/science.aaf3646 · Cited by 230 · see citing works
Cien Años de Microglía: Milestones in a Century of Microglial Research
Sierra, A., Paolicelli, R. C., & Kettenmann, H. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.09.004 · Cited by 229 · see citing works
Qin, J., Ma, Z., Chen, X., & Shu, S. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1103416 · Cited by 229 · see citing works
A distinct population of microglia supports adult neurogenesis in the subventricular zone
Ribeiro Xavier, A. L., Kress, B. T., Goldman, S. A., Lacerda de Menezes, J. R., & Nedergaard, M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1217-15.2015 · Cited by 225 · see citing works
Insulin-Like Growth Factor-1 and Neuroinflammation
Labandeira-García, J. L., Costa-Besada, M. A., Labandeira, C. M., Villar‐Cheda, B., & Rodriguez-Perez, A. I. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00365 · Cited by 224 · see citing works
Microglia function during brain development: New insights from animal models
Bilimoria, P. M., & Stevens, B. (2015) · Brain Research · doi:10.1016/j.brainres.2014.11.032 · Cited by 204 · see citing works
Xu, R., Boreland, A. J., Li, X., Erickson, C., Jin, M., Atkins, C., Pang, Z. P., Daniels, B. P., & Jiang, P. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.06.011 · Cited by 222 · see citing works
Interactions of innate and adaptive immunity in brain development and function
Filiano, A. J., Gadani, S. P., & Kipnis, J. (2014) · Brain Research · doi:10.1016/j.brainres.2014.07.050 · Cited by 217 · see citing works
Microglia in multiple sclerosis: Friend or foe
Guerrero, B. L., & Sicotte, N. L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00374 · Cited by 215 · see citing works
Liu, W., Taso, O., Wang, R., Bayram, S., Graham, A. C., Garcia-Reitboeck, P., Mallach, A., Andrews, W. D., Piers, T. M., Botia, J. A., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa209 · Cited by 214 · see citing works
“Igf1 is abundantly expressed by microglia during postnatal development, aging, or following brain injuries and plays a vital role in promoting neuronal survival (Fernandez and Torres-Aleman 2012; Kohman et al. 2012; Thored et al. 2009; Ueno et al. 2013).”
BackgroundMicroglia in Brain Development, Homeostasis, and Neurodegeneration
Bohlen, C. J., Friedman, B. A., Dejanovic, B., & Sheng, M. (2019) · Annual Review of Genetics · doi:10.1146/annurev-genet-112618-043515 · Cited by 212 · see citing works
Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan
Tay, T. L., Béchade, C., D’Andrea, I., St‐Pierre, M., Henry, M. S., Roumier, A., & Tremblay, M. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00421 · Cited by 211 · see citing works
Modulating neurotoxicity through CX3CL1/CX3CR1 signaling
Limatola, C., & Ransohoff, R. M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00229 · Cited by 210 · see citing works
It Takes a Village: Constructing the Neurogenic Niche
Bjornsson, C. S., Apostolopoulou, M., Tian, Y. I., & Temple, S. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.01.010 · Cited by 210 · see citing works
Zabel, M. K., Zhao, L., Zhang, Y., Gonzalez, S. R., Ma, W., Wang, X., Fariss, R. N., & Wong, W. T. (2016) · Glia · doi:10.1002/glia.23016 · Cited by 210 · see citing works
Endo, F., Komine, O., Fujimori-Tonou, N., Katsuno, M., Jin, S., Watanabe, S., Sobue, G., Dezawa, M., Wyss-Coray, T., & Yamanaka, K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.053 · Cited by 207 · see citing works
The Role of Microglia and Macrophages in CNS Homeostasis, Autoimmunity, and Cancer
Yin, J., Valin, K. L., Dixon, M. L., & Leavenworth, J. W. (2017) · Journal of Immunology Research · doi:10.1155/2017/5150678 · Cited by 206 · see citing works
Macrophage Clearance of Apoptotic Cells: A Critical Assessment
Gordon, S., & Plüddemann, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00127 · Cited by 201 · see citing works
Microglia: Multitasking Specialists of the Brain
Casano, A. M., & Peri, F. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.01.018 · Cited by 192 · see citing works
Nemes-Baran, A. D., White, D. R., & DeSilva, T. M. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108047 · Cited by 196 · see citing works
Parodi, B., Rossi, S., Morando, S., Cordano, C., Bragoni, A., Motta, C., Usai, C., Wipke, B. T., Scannevin, R. H., Mancardi, G., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1422-3 · Cited by 196 · see citing works
IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge
Spadaro, O., Camell, C. D., Bosurgi, L., Nguyen, K., Youm, Y., Rothlin, C. V., & Dixit, V. D. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.046 · Cited by 196 · see citing works
Early life stress perturbs the maturation of microglia in the developing hippocampus
Delpech, J.-C., Wei, L., Hao, J., Yu, X., Madore, C., Butovsky, O., & Kaffman, A. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.06.006 · Cited by 193 · see citing works
Sabaté‐Soler, S., Nickels, S., Saraiva, C., Berger, E., Dubonyte, U., Barmpa, K., Lan, Y. J., Kouno, T., Jarazo, J., Robertson, G., et al. (2022) · Glia · doi:10.1002/glia.24167 · Cited by 191 · see citing works
Sex differences in microglial phagocytosis in the neonatal hippocampus
Nelson, L. H., Warden, S., & Lenz, K. M. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.03.010 · Cited by 189 · see citing works
Silencing of TGFβ signalling in microglia results in impaired homeostasis
Zöller, T., Schneider, A., Kleimeyer, C., Masuda, T., Potru, P. S., Pfeifer, D., Blank, T., Prinz, M., & Spittau, B. (2018) · Nature Communications · doi:10.1038/s41467-018-06224-y · Cited by 189 · see citing works
Efficient Strategies for Microglia Replacement in the Central Nervous System
Xu, Z., Rao, Y., Huang, Y., Zhou, T. G., Feng, R., Xiong, S., Yuan, T., Qin, S., Lu, Y., Zhou, X., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108041 · Cited by 184 · see citing works
Role of the Immune System in the Development of the Central Nervous System
Morimoto, K., & Nakajima, K. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00916 · Cited by 181 · see citing works
- Authors
- Ueno, M., Fujita, Y., Tanaka, T., Nakamura, Y., Kikuta, J., Ishii, M., & Yamashita, T.
- Affiliations
- Japan Science and Technology Agency (JP)
- Asahikawa Medical University (JP)
- Immunology Frontier Research Center, The University of Osaka (JP)
- Corresponding author
- Ueno, Masaki
- Yamashita, Toshihide
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2013-03-24
- Volume
- 16
- Issue
- 5
- Pages
- 543-551
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2015412022
- Cited by
- 781
- References
- 50
- Citations by year
- 2026: 41 · 2025: 54 · 2024: 67 · 2023: 61 · 2022: 65 · 2021: 81 · 2020: 82 · 2019: 69 · 2018: 64 · 2017: 52 · 2016: 50 · 2015: 43 · 2014: 41 · 2013: 11
- FWCI
- 26.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- 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, neuronal survival, postnatal brain development, insulin-like growth factor I, trophic support, neuron-glia interactions, CX3CR1, apoptosis, minocycline, callosal projection neurons, microglial activation
- MeSH terms
- CX3C Chemokine Receptor 1, Animals, Animals, Newborn, Calcium-Binding Proteins, Cell Survival, Cells, Cultured, Diphtheria Toxin, Embryo, Mammalian, Enzyme Inhibitors, Humans, Insulin-Like Growth Factor I, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins, Nerve Tissue Proteins, Neurons, Visual Cortex, Apoptosis, Microglia, Gene Expression Regulation, Developmental, Coculture Techniques, Receptors, Chemokine, CD11b Antigen, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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