Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor
Open accessAbstract
Microglia are the resident macrophages of the CNS, and their functions have been extensively studied in various brain pathologies. The physiological roles of microglia in brain plasticity and function, however, remain unclear. To address this question, we generated CX3CR1(CreER) mice expressing tamoxifen-inducible Cre recombinase that allow for specific manipulation of gene function in microglia. Using CX3CR1(CreER) to drive diphtheria toxin receptor expression in microglia, we found that microglia could be specifically depleted from the brain upon diphtheria toxin administration. Mice depleted of microglia showed deficits in multiple learning tasks and a significant reduction in motor-learning-dependent synapse formation. Furthermore, Cre-dependent removal of brain-derived neurotrophic factor (BDNF) from microglia largely recapitulated the effects of microglia depletion. Microglial BDNF increases neuronal tropomyosin-related kinase receptor B phosphorylation, a key mediator of synaptic plasticity. Together, our findings reveal that microglia serve important physiological functions in learning and memory by promoting learning-related synapse formation through BDNF signaling.
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BDNF is widely expressed in neurons, astrocytes, and microglia, with microglia regarded as the primary source of BDNF.
“BDNF is widely expressed in neurons, astrocytes, and microglia, among which microglia are regarded as the primary source of BDNF (162).”
From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [162]
The Discussion section confirms that BDNF can be detected in neurons, astrocytes, and microglia. But it explicitly says that neurons, not microglia, appear to be the major source of BDNF in the adult brain. (LLM, conf=0.95)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredNo leakiness was reported in those studies using the YFP reporter line to verify two inducible Cx3cr1-CreERT2 lines.
“No leakiness was reported in those studies.”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Parkhurst et al., 2013
The Results section, “Generation of CX3CR1CreER mice to manipulate gene expression in microglia” (page not available), reports DsRed-positive microglia even without tamoxifen, contrary to the claim that no leakiness was reported. EYFP marked cells expressing the CreER transcript; the paper used a DsRed reporter to test Cre-mediated recombination. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn the CX3CR1CreER-iresGFP/+;Rosa26stop-DsRed system, CNS microglia retain DsRed expression 30 days after tamoxifen whereas peripheral macrophages do not due to ongoing turnover; both cell types constitutively express GFP.
“In this system, CNS microglia retain their DsRed expression 30 days after tamoxifen treatment whereas peripheral macrophages do not due to ongoing turnover; both cell types constitutively express GFP under control of the CX3CR1 promoter (Parkhurst et al., 2013).”
From Activated microglia drive demyelination via <scp>CSF1R</scp> signaling (2021) · cites this paper as Parkhurst et al., 2013
The Results section ('Cre-dependent manipulation of gene expression in microglia') reports that 93.0% of microglia remained DsRed+ 30 days after tamoxifen, versus 7.9% of spleen cells and 1.7% of blood cells, and explains the difference by peripheral-cell turnover. But 'Generation of CX3CR1CreER mice' identifies the constitutive reporter as IRES-EYFP, not GFP; peripheral DsRed expression was low, not absent. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe majority of peripheral immune cells that express Cx3cr1 are short lived and turn over within 4 weeks because of ongoing, lifelong hematopoiesis.
“However, the majority of these peripheral cells are short lived and turn over within 4 weeks because of ongoing, lifelong hematopoiesis.10–12”
From A comparative analysis of microglial inducible Cre lines (2023) · cites this paper as [10]
In Results, under “Cre-dependent manipulation of gene expression in microglia” (page not available), the paper says peripheral CX3CR1+ populations are replaced from bone-marrow precursors and reports that few blood and spleen cells retained the recombination marker 30 days after tamoxifen treatment. This supports rapid turnover, but the experiment used young mice and does not establish turnover within exactly four weeks or that the process continues throughout life. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe YFP reporter line was used to verify two inducible Cx3cr1-CreERT2 lines (Jung et al., 2000; Parkhurst et al., 2013).
“The YFP reporter line was used to verify two inducible Cx3cr1-CreERT2 lines (Jung et al., 2000; Parkhurst et al., 2013).”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Parkhurst et al., 2013
The Results section, “Generation of CX3CR1CreER mice” (page not provided), describes one inducible line with a built-in EYFP element and uses EYFP to assess its expression. It does not say that a separate YFP reporter line verified two inducible lines; Cre activity was tested with a DsRed reporter instead. (LLM, conf=0.87)
Experimental — accuracy not yet measured
In the brain, BDNF is expressed by glutamatergic neurons, astrocytes isolated from the cortex and hippocampus but not from the striatum, and microglia.
“In the brain, BDNF is expressed by glutamatergic neurons [1], glial cells, such as astrocytes isolated from the cortex and hippocampus, but not from the striatum [2], and microglia [3].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [3]
The inducible Cx3cr1-CreERT2 mouse line developed by Parkhurst et al. displayed a reasonable level of microglial-specificity in their hands.
“The inducible Cx3cr1-CreERT2 mouse line that was developed by Parkhurst et al., displayed a reasonable level of microglial-specificity in their hands (Parkhurst et al., 2013).”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Parkhurst et al., 2013
No spontaneous seizures were observed in the Zhang et al. (2018) study that used the Parkhurst Cx3cr1-CreERT2 line.
“In contrast, no spontaneous seizures were observed in the other study (Zhang et al., 2018) that used the Cx3cr1-CreERT2 mouse line developed by Parkhurst et al. (2013).”
From Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity (2019) · cites this paper as Parkhurst et al. (2013)
Reduced time spent in the center zone is considered to be a marker of anxiety-like behavior.
“Reduced time spent in the center zone is considered to be a marker of anxiety-like behavior8,21.”
From Constitutive expression of CX3CR1-BAC-Cre introduces minimal off-target effects in microglia (2026) · cites this paper as [21]
The Behavioral testing protocols section lists rotarod training, cue-based fear conditioning, and novel object recognition, but does not discuss time spent in a center zone. Searches for center-zone time, anxiety-like behavior, and open-field testing found no passage in our copy addressing the claimed marker. (LLM, conf=0.72)
Experimental — accuracy not yet measuredDepletion of microglia in mice engineered to express diphtheria toxin receptor in microglia caused a significant reduction in motor-learning-dependent glutamatergic excitatory synapses and impaired performance in multiple learning tasks, and this plasticity depended on BDNF secretion activating neuronal Trk.
“Administration of DT and subsequent depletion of microglia in these mice caused a significant reduction in motor-learning-dependent glutamatergic excitatory synapses and impaired performance in multiple learning tasks. In this model, microglia-induced synaptic plasticity depended on BDNF secretion, which activated neuronal Trk, a key mediator of synaptic plasticity (Figure 2).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [77]
Microglia secrete neurotrophic factors NGF, BDNF, NT3, FGF, and IGF1 that control receptor tyrosine kinase activity and PI3K signalling, and microglia promote learning-dependent synapse formation via BDNF in mice.
“Microglia secrete neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), fibroblast growth factor (FGF) and insulin-like growth factor 1 (IGF1), that control the activity of receptor tyrosine kinases and are associated with signalling through phosphoinositide 3-kinase (PI3K)94.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [96]
Depletion of microglia by genetic expression of diphtheria toxin could lead to deficits in learning and contextual fear conditioning, or cause cytokine expression in the brain.
“Depletion of microglia by genetic expression of diphtheria toxin could lead to deficits in learning and contextual fear conditioning39, or cause cytokine expression in the brain31, whereas toxicity to hematopoietic cells was observed in CD11b-HSVTK mice in response to ganciclovir40.”
From Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke (2016) · cites this paper as [39]
4-hydroxytamoxifen treatment in young adult double transgenic offspring results in robust elimination of basal ganglia microglia.
“4-hydroxytamoxifen (4HT) treatment in young adult, double transgenic offspring resulted in robust elimination of BG microglia”
From Local cues establish and maintain region-specific phenotypes of basal ganglia microglia (2017) · cites this paper as Parkhurst et al., 2013
Microglial-derived inflammatory and trophic signaling factors impact formation and elimination of dendritic spines.
“which have been shown to impact formation and elimination of dendritic spines (Parkhurst et al., 2013)”
From Local cues establish and maintain region-specific phenotypes of basal ganglia microglia (2017) · cites this paper as Parkhurst et al., 2013
The Cx3cr1CreErt2/+(Litt) line was chosen for later experiments because its Cre expression is microglia-specific and highly efficient (>99% of microglia) across the brain.
“The Cx3cr1CreErt2/+(Litt)52 line was selected for all subsequent experiments due to its highly efficient (>99% of microglia) and microglia-specific Cre expression pattern throughout the brain.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [52]
Microglia can elicit calcium transients and formation of filopodia from dendritic branches, and are required for learning-induced synapse formation.
“At the same time, studies have pointed to a role for microglia in synapse formation in the adult brain, showing that they can elicit calcium transients and the formation of filopodia from dendritic branches15, and that they are required for learning-induced synapse formation16.”
From Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction (2018) · cites this paper as [16]
The release of BDNF by microglial cells induces synaptic pruning; depletion of this factor in microglia results in learning and memory impairment.
“The release of brain-derived neurotrophic factor (BDNF) by microglial cells induces synaptic pruning. However, the depletion of this factor in the microglia results in learning and memory impairment (Parkhurst et al., 2013).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Parkhurst et al., 2013
Depletion of microglia results in significant reduction of motor learning induced spine formation.
“In addition, the depletion of microglia resulted in significant reduction of motor learning induced spine formation, and selective removal of brain-derived neurotrophic factor (BDNF) in microglia recapitulated the effects of microglial depletion (Parkhurst et al., 2013).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Parkhurst et al., 2013
Selective removal of BDNF in microglia recapitulates the effects of microglial depletion on motor learning induced spine formation.
“In addition, the depletion of microglia resulted in significant reduction of motor learning induced spine formation, and selective removal of brain-derived neurotrophic factor (BDNF) in microglia recapitulated the effects of microglial depletion (Parkhurst et al., 2013).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Parkhurst et al., 2013
BDNF activates neuronal TrkB that regulates synaptic plasticity and modulates glutamatergic synaptic transmission in vivo and neuronal LTP.
“BDNF has been shown to activate neuronal Tropomyosin-related kinase receptor B (TrkB) that regulates synaptic plasticity and modulate glutamatergic synaptic transmission in vivo and neuronal LTP, which is a key feature of memory formation and consolidation (Parkhurst et al., 2013; Lai et al., 2018).”
From miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A (2020) · cites this paper as Parkhurst et al., 2013
Microglia-derived BDNF contributes to maintenance of synaptic plasticity.
“microglia derived factors such as BDNF, have been shown to contribute to the maintenance of synaptic plasticity (Harada et al., 2002; Parkhurst et al., 2013).”
From miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A (2020) · cites this paper as Parkhurst et al., 2013
Microglial BDNF contributes to learning-dependent synapse formation.
“Of note, a recent study reported the significant contribution of microglial brain-derived neurotrophic factor (BDNF) towards learning-dependent synapse formation (Parkhurst et al., 2013; Saw et al., 2020).”
From miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A (2020) · cites this paper as Parkhurst et al., 2013
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Cites
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
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395 · 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
Large-scale analysis of the yeast proteome by multidimensional protein identification technology
Washburn, M. P., Wolters, D. A., & Yates, J. R. (2001) · Nature Biotechnology · doi:10.1038/85686 · Cited by 4,759 · see citing works
Self-citationSynaptic 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
Microglia 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 addition, the microglia themselves express activated TrkB, and BDNF released from microglia has been shown to increase their proliferation (Spencer-Segal et al., 2011).”
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 · see citing works
Self-citationJung, 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
Self-citationGray, E. G., & Whittaker, V. P. (1962) · PubMed · Cited by 2,530 · see citing works
Neurotrophins and their receptors: A convergence point for many signalling pathways
Chao, M. V. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1078 · Cited by 2,298 · see citing works
BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain
Coull, J. A. M., Beggs, S., Boudreau, D., Boivin, D., Tsuda, M., Inoue, K., Gravel, C., Salter, M. W., & De Koninck, Y. (2005) · Nature · doi:10.1038/nature04223 · Cited by 1,965 · see citing works
Local self-renewal can sustain CNS microglia maintenance and function throughout adult life
Ajami, B., Bennett, J. L., Krieger, C., Tetzlaff, W., & Rossi, F. M. V. (2007) · Nature Neuroscience · doi:10.1038/nn2014 · Cited by 1,643 · 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 ORIGIN AND KINETICS OF MONONUCLEAR PHAGOCYTES
van Furth, R., & Cohn, Z. A. (1968) · The Journal of Experimental Medicine · doi:10.1084/jem.128.3.415 · Cited by 1,564 · see citing works
Microglial 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 · see citing works
Bevins, R. A., & Besheer, J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.205 · Cited by 1,278 · see citing works
Long-term dendritic spine stability in the adult cortex
Grutzendler, J., Kasthuri, N., & Gan, W.-B. (2002) · Nature · doi:10.1038/nature01276 · Cited by 1,198 · cited 1× · see citing works
“Many lines of evidence indicate that experience-dependent synaptic structural plasticity is important for CNS development, as well as for learning andmemory formation (Bailey and Kandel, 1993; Grutzendler et al., 2002; Yang et al., 2009a).”
BackgroundSelf-citationStably maintained dendritic spines are associated with lifelong memories
Yang, G., Pan, F., & Gan, W.-B. (2009) · Nature · doi:10.1038/nature08577 · Cited by 1,182 · see citing works
Self-citationA Clonogenic Bone Marrow Progenitor Specific for Macrophages and Dendritic Cells
Fogg, D. K., Sibon, C., Miled, C., Jung, S., Aucouturier, P., Littman, D. R., Cumano, A., & Geissmann, F. (2005) · Science · doi:10.1126/science.1117729 · Cited by 1,050 · see citing works
Self-citationA Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration
Buch, T., Heppner, F. L., Tertilt, C., Heinen, T. J. A. J., Kremer, M., Wunderlich, F. T., Jung, S., & Waisman, A. (2005) · Nature Methods · doi:10.1038/nmeth762 · Cited by 922 · see citing works
Structural Changes Accompanying Memory Storage
Bailey, C. H., & Kandel, E. R. (1993) · Annual Review of Physiology · doi:10.1146/annurev.ph.55.030193.002145 · Cited by 856 · see citing works
Rios, M., Fan, G., Fekete, C., Kelly, J., Bates, B., Kuehn, R., Lechan, R. M., & Jaenisch, R. (2001) · Molecular Endocrinology · doi:10.1210/mend.15.10.0706 · Cited by 781 · 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
Turnover 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
Peri, F., & Nüsslein-Volhard, C. (2008) · Cell · doi:10.1016/j.cell.2008.04.037 · Cited by 617 · see citing works
Wild-type microglia arrest pathology in a mouse model of Rett syndrome
Derecki, N. C., Cronk, J. C., Lu, Z., Xu, E., Abbott, S. B. G., Guyenet, P. G., & Kipnis, J. (2012) · Nature · doi:10.1038/nature10907 · Cited by 607 · see citing works
New Insights in the Biology of BDNF Synthesis and Release: Implications in CNS Function
Greenberg, M. E., Xu, B., Lu, B., & Hempstead, B. L. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3566-09.2009 · Cited by 597 · see citing works
Self-citationReciprocal Regulation between Resting Microglial Dynamics and Neuronal Activity In Vivo
Li, Y., Du, X.-F., Liu, C., Wen, Z., & Du, J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.10.027 · Cited by 553 · see citing works
Luche, H., Weber, O., Nageswara Rao, T., Blum, C., & Fehling, H. J. (2007) · European Journal of Immunology · doi:10.1002/eji.200636745 · Cited by 482 · see citing works
Trang, T., Beggs, S., Wan, X., & Salter, M. W. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5714-08.2009 · Cited by 474 · see citing works
Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts
Paloneva, J., Kestilä, M., Wu, J., Salminen, A., Böhling, T., Ruotsalainen, V., Hakola, P., Bakker, A. B. H., Phillips, J. H., Pekkarinen, P., et al. (2000) · Nature Genetics · doi:10.1038/77153 · Cited by 460 · 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
Yang, J., Siao, C.-J., Nagappan, G., Marinic, T., Jing, D., McGrath, K., Chen, Z.-Y., Mark, W., Tessarollo, L., Lee, F. S., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2244 · Cited by 449 · see citing works
Self-citationInducible gene targeting in the neonatal vasculature and analysis of retinal angiogenesis in mice
Pitulescu, M. E., Schmidt, I., Benedito, R., & Adams, R. H. (2010) · Nature Protocols · doi:10.1038/nprot.2010.113 · Cited by 418 · see citing works
Levine, E. S., Crozier, R. A., Black, I. B., & Plummer, M. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.10235 · Cited by 412 · see citing works
Opposite effects of fear conditioning and extinction on dendritic spine remodelling.
Lai, C. S. W., Franke, T. F., & Gan, W.-B. (2012) · Nature · doi:10.1038/nature10792 · Cited by 392 · see citing works
Self-citationHoshiko, M., Arnoux, I., Avignone, E., Yamamoto, N., & Audinat, E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1167-12.2012 · Cited by 384 · cited 1× · see citing works
“Recent work has shown that mice lackingCX3CR1 have delayed invasion of the cortical barrel fields by microglia, and a transient delay in the normally observed AMPA receptor subunit switching in thalamocortical barrel cortex synapses (Hoshiko et al., 2012).”
BackgroundDougherty, K. D., Dreyfus, C., & Black, I. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0318 · Cited by 373 · see citing works
Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance.
Liston, C., Cichon, J. M., Jeanneteau, F., Jia, Z., Chao, M. V., & Gan, W.-B. (2013) · Nature Neuroscience · doi:10.1038/nn.3387 · Cited by 358 · see citing works
Self-citationNeuromodulation by Extracellular ATP and P2X Receptors in the CNS
Khakh, B. S., & North, R. A. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.024 · Cited by 343 · see citing works
Extremely long-lived nuclear pore proteins in the rat brain
Savas, J. N., Toyama, B. H., Xu, T., Yates, J. R., & Hetzer, M. W. (2012) · Science · doi:10.1126/science.1217421 · Cited by 335 · see citing works
Self-citationBałkowiec, A., & Katz, D. M. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-19-07417.2000 · Cited by 332 · see citing works
Rex, C. S., Lin, C.-Y., Kramár, E. A., Chen, L. Y., Gall, C. M., & Lynch, G. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4037-06.2007 · Cited by 324 · see citing works
Rauskolb, S., Zagrebelsky, M., Dreznjak, A., Deogracias, R., Matsumoto, T., Wiese, S., Erne, B., Sendtner, M., Schaeren‐Wiemers, N., Körte, M., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5100-09.2010 · Cited by 289 · see citing works
Subtype-Dependence of NMDA Receptor Channel Open Probability
Chen, N., Luo, T., & Raymond, L. A. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-16-06844.1999 · Cited by 260 · see citing works
Impaired Synaptic Function in the Microglial KARAP/DAP12-Deficient Mouse
Roumier, A., Béchade, C., Poncer, J. C., Smalla, K., Tomasello, E., Vivier, É., Gundelfinger, E. D., Triller, A., & Bessis, A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2251-04.2004 · Cited by 228 · see citing works
Swinnen, N., Smolders, S., Ávila, A., Notelaers, K., Paesen, R., Ameloot, M. M., Brône, B., Legendre, P., & Rigo, J. (2012) · Glia · doi:10.1002/glia.22421 · Cited by 226 · see citing works
Activation of Trk neurotrophin receptors by glucocorticoids provides a neuroprotective effect
Jeanneteau, F., Garabedian, M. J., & Chao, M. V. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709102105 · Cited by 215 · see citing works
Pattwell, S. S., Bath, K. G., Perez-Castro, R., Lee, F. S., Chao, M. V., & Ninan, I. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5205-11.2012 · Cited by 156 · see citing works
Self-citationCSF-1 deficiency in mice results in abnormal brain development
Michaelson, M. D., Bieri, P. L., Mehler, M. F., Xu, H., Arezzo, J. C., Pollard, J. W., & Kessler, J. A. (1996) · Development · doi:10.1242/dev.122.9.2661 · Cited by 129 · see citing works
Expression of the BDNF gene in the developing visual system of the chick
Herzog, K., Bailey, K. A., & Barde, Y. (1994) · Development · doi:10.1242/dev.120.6.1643 · Cited by 93 · see citing works
Spencer-Segal, J. L., Waters, E. M., Bath, K. G., Chao, M. V., McEwen, B. S., & Milner, T. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0910-11.2011 · Cited by 92 · see citing works
Zheng, K., An, J. J., Yang, F., Xu, W., Xu, Q., Wu, J., Hökfelt, T. G. M., Fisahn, A., Xu, B., & Lu, B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114241108 · Cited by 82 · see citing works
Chakravarthy, S., Saiepour, M. H., Bence, M., Perry, S., Hartman, R., Couey, J. J., Mansvelder, H. D., & Levelt, C. N. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506305103 · Cited by 79 · see citing works
Melo, C. V., Mele, M., Curcio, M., Comprido, D., Silva, C. G., & Duarte, C. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053793 · Cited by 63 · see citing works
Butko, M. T., Savas, J. N., Friedman, B., Delahunty, C. M., Ebner, F. F., Yates, J. R., & Tsien, R. Y. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300424110 · Cited by 60 · see citing works
Self-citationEnglish, C. N., Vigers, A. J., & Jones, K. R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206492109 · Cited by 36 · see citing works
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Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · see citing works
Microglia Function in the Central Nervous System During Health and Neurodegeneration
Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894 · see citing works
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134 · see citing works
How neuroinflammation contributes to neurodegeneration
Ransohoff, R. M. (2016) · Science · doi:10.1126/science.aag2590 · Cited by 1,967 · see citing works
Elmore, 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
New tools for studying microglia in the mouse and human CNS
Bennett, M. L., Bennett, F. C., Liddelow, S. A., Ajami, B., Zamanian, J. L., Fernhoff, N. B., Mulinyawe, S. B., Bohlen, C. J., Adil, A., Tucker, A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525528113 · Cited by 1,804 · see citing works
Microglia emerge as central players in brain disease
Salter, M. W., & Stevens, B. (2017) · Nature Medicine · doi:10.1038/nm.4397 · Cited by 1,767 · 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 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
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
Different immune cells mediate mechanical pain hypersensitivity in male and female mice
Sorge, R. E., Mapplebeck, J. C. S., Rosen, S., Beggs, S., Taves, S., Alexander, J. K., Martin, L. J., Austin, J.-S., Sotocinal, S. G., Chen, D., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4053 · Cited by 1,442 · see citing works
Innate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437 · see citing works
Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease
Prinz, M., & Priller, J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3722 · Cited by 1,329 · see citing works
An environment-dependent transcriptional network specifies human microglia identity
Gosselin, D., Skola, D., Coufal, N. G., Holtman, I. R., Schlachetzki, J. C. M., Sajti, E., Jaeger, B. N., O’Connor, C., Fitzpatrick, C., Pasillas, M. P., et al. (2017) · Science · doi:10.1126/science.aal3222 · Cited by 1,220 · see citing works
13 reasons why the brain is susceptible to oxidative stress
Cobley, J. N., Fiorello, M. L., & Bailey, D. M. (2018) · Redox Biology · doi:10.1016/j.redox.2018.01.008 · Cited by 1,215 · see citing works
Microglial signatures and their role in health and disease
Butovsky, O., & Weiner, H. L. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0057-5 · Cited by 1,046 · see citing works
Colucci-D’Amato, L., Speranza, L., & Volpicelli, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207777 · Cited by 991 · see citing works
Astrocyte reactivity and reactive astrogliosis: costs and benefits
Pekny, M., & Pekna, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2013 · Cited by 934 · see citing works
Depression as a Microglial Disease
Yirmiya, R., Rimmerman, N., & Reshef, R. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.001 · Cited by 944 · see citing works
Microglia polarization from M1 to M2 in neurodegenerative diseases
Guo, S., Wang, H., & Yin, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.815347 · Cited by 920 · see citing works
Dual microglia effects on blood brain barrier permeability induced by systemic inflammation
Haruwaka, K., Ikegami, A., Tachibana, Y., Ohno, N., Konishi, H., Hashimoto, A., Matsumoto, M., Kato, D., Ono, R., Kiyama, H., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13812-z · Cited by 923 · see citing works
Self-Renewing Resident Cardiac Macrophages Limit Adverse Remodeling Following Myocardial Infarction
Dick, S. A., Macklin, J. A., Nejat, S., Momen, A., Clemente-Casares, X., Althagafi, M. G., Chen, J., Kantores, C., Hosseinzadeh, S., Aronoff, L., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0272-2 · Cited by 883 · see citing works
Microglia in Alzheimer's disease
Sarlus, H., & Heneka, M. T. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90606 · Cited by 911 · see citing works
Inflammation and neuroprotection in traumatic brain injury.
Corps, K. N., Roth, T. L., & McGavern, D. B. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2014.3558 · Cited by 853 · see citing works
Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.010 · Cited by 799 · see citing works
Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction
Weinhard, L., di Bartolomei, G., Bolasco, G., Machado, P., Schieber, N. L., Neniskyte, U., Exiga, M., Vadisiute, A., Raggioli, A., Schertel, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03566-5 · Cited by 790 · 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
Lui, H., Zhang, J., Makinson, S. R., Cahill, M. K., Kelley, K. W., Huang, H.-Y., Shang, Y., Oldham, M. C., Martens, L. H., Gao, F., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.001 · Cited by 729 · see citing works
TREM2 — a key player in microglial biology and Alzheimer disease
Ulland, T. K., & Colonna, M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0072-1 · Cited by 735 · see citing works
Integrating neuroimmune systems in the neurobiology of depression
Wohleb, E. S., Franklin, T., Iwata, M., & Duman, R. S. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.69 · Cited by 668 · see citing works
Bruttger, J., Karram, K., Wörtge, S., Regen, T., Marini, F., Hoppmann, N., Klein, M., Blank, T., Yona, S., Wolf, Y., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.012 · Cited by 634 · see citing works
Microglia: Dynamic Mediators of Synapse Development and Plasticity
Wu, Y., Dissing-Olesen, L., MacVicar, B. A., & Stevens, B. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.008 · Cited by 661 · see citing works
Microglia contact induces synapse formation in developing somatosensory cortex
Miyamoto, A., Wake, H., Ishikawa, A. W., Eto, K., Shibata, K., Murakoshi, H., Koizumi, S., Moorhouse, A. J., Yoshimura, Y., & Nabekura, J. (2016) · Nature Communications · doi:10.1038/ncomms12540 · Cited by 649 · see citing works
Vainchtein, I. D., Chin, G., Cho, F. S., Kelley, K. W., Miller, J. G., Chien, E. C., Liddelow, S. A., Nguyen, P. T., Nakao-Inoue, H., Dorman, L. C., et al. (2018) · Science · doi:10.1126/science.aal3589 · Cited by 657 · see citing works
Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity
Nguyen, P. T., Dorman, L. C., Pan, S., Vainchtein, I. D., Han, R. T., Nakao-Inoue, H., Taloma, S. E., Barron, J. J., Molofsky, A. B., Kheirbek, M. A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.050 · Cited by 615 · see citing works
TAM receptors regulate multiple features of microglial physiology
Fourgeaud, L., Través, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagórska, A., Rothlin, C. V., Nimmerjahn, A., et al. (2016) · Nature · doi:10.1038/nature17630 · Cited by 600 · see citing works
RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS
Ito, Y., Ofengeim, D., Najafov, A., Das, S., Saberi, S., Li, Y., Hitomi, J., Zhu, H., Chen, H., Mayo, L., et al. (2016) · Science · doi:10.1126/science.aaf6803 · Cited by 606 · see citing works
Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice
Shi, Q., Chowdhury, S., Ma, R., Le, K. X., Hong, S., Caldarone, B. J., Stevens, B., & Lemere, C. A. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf6295 · Cited by 593 · see citing works
“Furthermore, mice deficient in BDNF in microglia have deficits in learning andhippocampal synapse formation, indicating thatmicroglial BDNF signaling plays an important role in hippocampal function (60).”
BackgroundSall1 is a transcriptional regulator defining microglia identity and function
Buttgereit, A., Lelios, I., Yu, X., Vrohlings, M., Krakoski, N. R., Gautier, E. L., Nishinakamura, R., Becher, B., & Greter, M. (2016) · Nature Immunology · doi:10.1038/ni.3585 · Cited by 570 · 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
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
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
A new fate mapping system reveals context-dependent random or clonal expansion of microglia
Tay, T. L., Mai, D., Dautzenberg, J., Fernández-Klett, F., Lin, G., Sagar, Datta, M., Drougard, A., Stempfl, T., Ardura-Fabregat, A., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4547 · Cited by 597 · see citing works
Szalay, G., Martinecz, B., Lénárt, N., Környei, Z., Orsolits, B., Judák, L., Császár, E., Fekete, R., West, B. L., Katona, G., et al. (2016) · Nature Communications · doi:10.1038/ncomms11499 · Cited by 573 · 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
Huang, Y., Xu, Z., Xiong, S., Sun, F., Qin, G., Hu, G., Wang, J., Zhao, L., Liang, Y.-X., Wu, T., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0090-8 · Cited by 560 · see citing works
Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration
Choi, I., Zhang, Y., Seegobin, S. P., Pruvost, M., Wang, Q., Purtell, K., Zhang, B., & Yue, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-15119-w · Cited by 549 · 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
The Lifespan and Turnover of Microglia in the Human Brain
Réu, P., Khosravi, A., Bernard, S., Mold, J. E., Salehpour, M., Alkass, K., Perl, S., Tisdale, J., Possnert, G., Druid, H., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.004 · Cited by 515 · see citing works
Lau, S.-F., Cao, H., Fu, A. K. Y., & Ip, N. Y. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2008762117 · Cited by 476 · see citing works
Inconsistencies and Controversies Surrounding the Amyloid Hypothesis of Alzheimer's Disease
Morris, G. P., Clark, I. A., & Vissel, B. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0135-5 · Cited by 522 · see citing works
Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner
Willis, E. F., MacDonald, K. P. A., Nguyen, Q. H., Garrido, A. L., Gillespie, E. R., Harley, S. B. R., Bartlett, P. F., Schroder, W. A., Yates, A. G., Anthony, D. C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.013 · Cited by 520 · see citing works
Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex
Sipe, G. O., Lowery, Tremblay, M.-È., Kelly, E. A., Lamantia, C. E., & Majewska, A. K. (2016) · Nature Communications · doi:10.1038/ncomms10905 · Cited by 512 · see citing works
Microglia in Central Nervous System Inflammation and Multiple Sclerosis Pathology
Voet, S., Prinz, M., & van Loo, G. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.11.005 · Cited by 503 · see citing works
Valdearcos, M., Douglass, J. D., Robblee, M. M., Dorfman, M. D., Stifler, D. R., Bennett, M. L., Gerritse, I., Fasnacht, R., Barres, B. A., Thaler, J. P., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.015 · Cited by 477 · see citing works
NBB-Psy, Böttcher, C., Schlickeiser, S., Sneeboer, M. A. M., Kunkel, D., Knop, A., Paza, E., Fidzinski, P., Kraus, L., Snijders, G. J. L., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0290-2 · Cited by 436 · 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
The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
Ramirez, A. I., de Hoz, R., Salobrar-Garcia, E., Salazar, J. J., Rojas, B., Ajoy, D., López-Cuenca, I., Rojas, P., Triviño, A., & Ramírez, J. M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00214 · Cited by 466 · see citing works
Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program
Geirsdottir, L., David, E., Keren-Shaul, H., Weiner, A., Bohlen, S. C., Neuber, J., Balic, A., Giladi, A., Sheban, F., Dutertre, C.-A., et al. (2019) · Cell · doi:10.1016/j.cell.2019.11.010 · Cited by 461 · see citing works
Epigenetic regulation of brain region-specific microglia clearance activity
Ayata, P., Badimon, A., Strasburger, H. J., Duff, M. K., Montgomery, S. E., Loh, Y.-H. E., Ebert, A., Pimenova, A. A., Ramirez, B. R., Chan, A. T., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0192-3 · Cited by 460 · see citing works
Lee, C. Y. D., Daggett, A., Gu, X., Jiang, L.-L., Langfelder, P., Li, X., Wang, N., Zhao, Y., Park, C. S., Cooper, Y., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.002 · Cited by 396 · see citing works
Local cues establish and maintain region-specific phenotypes of basal ganglia microglia
De Biase, L. M., Schuebel, K. E., Fusfeld, Z. H., Jair, K., Hawes, I. A., Cimbro, R., Zhang, H.-Y., Liu, Q.-R., Shen, H., Xi, Z.-X., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.06.020 · Cited by 432 · see citing works
Dark microglia: A new phenotype predominantly associated with pathological states
Bisht, K., Sharma, K. P., Lecours, C., Gabriela Sánchez, M., El Hajj, H., Milior, G., Olmos‐Alonso, A., Gómez‐Nicola, D., Luheshi, G., Vallières, L., et al. (2016) · Glia · doi:10.1002/glia.22966 · Cited by 421 · see citing works
Layé, S., Nadjar, A., Joffre, C., & Bazinet, R. P. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014092 · Cited by 420 · see citing works
Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases
Bartels, T., De Schepper, S., & Hong, S. (2020) · Science · doi:10.1126/science.abb8587 · Cited by 412 · see citing works
Microglia Priming with Aging and Stress
Niraula, A., Sheridan, J. F., & Godbout, J. P. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.185 · Cited by 398 · see citing works
Do glia drive synaptic and cognitive impairment in disease?
Chung, W.-S., Welsh, C. A., Barres, B. A., & Stevens, B. (2015) · Nature Neuroscience · doi:10.1038/nn.4142 · Cited by 385 · 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
Ensan, S., Li, A., Besla, R., Degousee, N., Cosme, J., Roufaiel, M., Shikatani, E. A., El-Maklizi, M., Williams, J. W., Robins, L., et al. (2016) · Nature Immunology · doi:10.1038/ni.3343 · Cited by 372 · 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
Zhong, L., Xu, Y., Zhuo, R., Wang, T., Wang, K., Huang, R., Wang, D., Gao, Y., Zhu, Y., Sheng, X., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09118-9 · Cited by 371 · see citing works
Yang, W., Tao, Y., Wu, Y., Zhao, X., Ye, W., Zhao, D., Fu, L., Tian, C., Yang, J., He, F., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09046-8 · Cited by 367 · see citing works
Microglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365 · see citing works
Liao, Y., Cheng, J., Kong, X., Li, S., Li, X., Zhang, M., Zhang, H., Yang, T., Dong, Y., Li, J., et al. (2020) · Theranostics · doi:10.7150/thno.47651 · Cited by 348 · see citing works
Microglial Physiology and Pathophysiology: Insights from Genome-wide Transcriptional Profiling
Crotti, A., & Ransohoff, R. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.013 · Cited by 323 · see citing works
Sankowski, R., Mader, S., & Valdés-Ferrer, S. I. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00028 · Cited by 351 · see citing works
Microglia Actively remodel adult hippocampal neurogenesis through the phagocytosis secretome
Diaz-Aparicio, I., Paris, I., Sierra-Torre, V., Plaza-Zabala, A., Rodríguez-Iglesias, N., Márquez-Ropero, M., Beccari, S., Huguet, P., Abiega, O., Alberdi, E., et al. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.0993-19.2019 · Cited by 333 · see citing works
Cellular Specificity of NF-κB Function in the Nervous System
Dresselhaus, E. C., & Meffert, M. K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01043 · Cited by 345 · 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
Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy
Wang, C., Fan, L., Khawaja, R. R., Liu, B., Zhan, L., Kodama, L., Chin, M., Li, Y., Le, D., Zhou, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29552-6 · Cited by 333 · see citing works
Neurobiology of local and intercellular BDNF signaling
Sasi, M., Vignoli, B., Canossa, M., & Blum, R. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1964-4 · Cited by 324 · see citing works
Cell-specific deletion of C1qa identifies microglia as the dominant source of C1q in mouse brain
Fonseca, M. I., Chu, S.-H., Hernandez, M. X., Fang, M. J., Modarresi, L., Selvan, P., MacGregor, G. R., & Tenner, A. J. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0814-9 · Cited by 337 · see citing works
Within the Brain: The Renin Angiotensin System
Jackson, L., Eldahshan, W., Fagan, S., & Ergul, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030876 · Cited by 336 · see citing works
Neuron-glia signaling in synapse elimination
Wilton, D. K., Dissing-Olesen, L., & Stevens, B. (2019) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070918-050306 · Cited by 332 · see citing works
Innate Immunity and Neurodegeneration
Labzin, L. I., Heneka, M. T., & Latz, E. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-050715-104343 · Cited by 319 · see citing works
Myelin plasticity: sculpting circuits in learning and memory
Xin, W., & Chan, J. R. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-00379-8 · Cited by 329 · see citing works
Microglia–blood vessel interactions: a double-edged sword in brain pathologies
Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F., & Schmidt, M. H. H. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1524-y · Cited by 301 · see citing works
Stowell, R. D., Sipe, G. O., Dawes, R. P., Batchelor, H. N., Lordy, K. A., Whitelaw, B. S., Stoessel, M. B., Bidlack, J. M., Brown, E., Sur, M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0514-0 · Cited by 321 · 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
Prada, I., Gabrielli, M., Turola, E., Iorio, A., D’Arrigo, G., Parolisi, R., De Luca, M., Pacifici, M., Bastoni, M., Lombardi, M., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-017-1803-x · Cited by 312 · see citing works
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
Kang, S. S., Ebbert, M. T. W., Baker, K. E., Cook, C., Wang, X., Sens, J. P., Kocher, J.-P., Petrucelli, L., & Fryer, J. D. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180653 · Cited by 260 · see citing works
“Comparison of RiboTag versus cell enrichment with sorting (referred to generally here as “cellular isolation”) methodologies for microglial transcript isolation was conducted in tamoxifen injected RiboTag mice, which induced Cx3cr1-YFP+-HA+ cells (Fig. S1 I; Parkhurst et al., 2013).”
BackgroundMethodRice, R. A., Spangenberg, E. E., Yamate-Morgan, H., Lee, R. J., Arora, R. P. S., Hernandez, M. X., Tenner, A. J., West, B. L., & Green, K. N. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0336-15.2015 · Cited by 270 · see citing works
Microglia Versus Myeloid Cell Nomenclature during Brain Inflammation
Greter, M., Lelios, I., & Croxford, A. L. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00249 · Cited by 273 · see citing works
Activation of Neuronal NMDA Receptors Triggers Transient ATP-Mediated Microglial Process Outgrowth
Dissing-Olesen, L., LeDue, J. M., Rungta, R. L., Hefendehl, J. K., Choi, H. B., & MacVicar, B. A. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0405-14.2014 · Cited by 286 · see citing works
Loss of adaptive myelination contributes to methotrexate chemotherapy-related cognitive impairment
Geraghty, A. C., Gibson, E. M., Ghanem, R. A., Greene, J. J., Ocampo, A., Goldstein, A. K., Ni, L., Yang, T., Marton, R. M., Paşca, S. P., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.04.032 · Cited by 288 · see citing works
IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis
Zhang, J., Rong, P., Zhang, L., He, H., Zhou, T., Fan, Y., Mo, L., Zhao, Q., Han, Y., Li, S., et al. (2021) · Science Advances · doi:10.1126/sciadv.abb9888 · Cited by 287 · see citing works
Garber, C., Soung, A., Vollmer, L. L., Kanmogne, M., Last, A., Brown, J., & Klein, R. S. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0427-y · Cited by 272 · see citing works
Deczkowska, A., Matcovitch-Natan, O., Tsitsou-Kampeli, A., Ben-Hamo, S., Dvir-Szternfeld, R., Spinrad, A., Singer, O., David, E., Winter, D. R., Smith, L. K., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00769-0 · Cited by 260 · see citing works
Hellwig, S., Brioschi, S., Dieni, S., Frings, L., Masuch, A., Blank, T., & Biber, K. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.11.008 · Cited by 252 · see citing works
- Authors
- 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.
- Affiliations
- New York University (US)
- NYU Langone Health (US)
- Scripps Research Institute (US)
- Weill Cornell Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Gan, Wen-Biao
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 155
- Issue
- 7
- Pages
- 1596-1609
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4033691
- OpenAlex
- W2096500024
- Cited by
- 2,599
- References
- 57
- Citations by year
- 2026: 148 · 2025: 202 · 2024: 252 · 2023: 230 · 2022: 276 · 2021: 264 · 2020: 297 · 2019: 204 · 2018: 208 · 2017: 175 · 2016: 145 · 2015: 112 · 2014: 78
- FWCI
- 62.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute on Aging (F32AG039127, P01AG031097)
- National Institute of Mental Health (R01MH067880, R01MH096899, R01 MH96899, R56MH096899, F30MH096370)
- National Institute of General Medical Sciences (P41GM103533)
- National Institute of Neurological Disorders and Stroke (R01NS047325, NS030687, P01NS074972, R01NS030687, R01NS087198)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microglia, brain-derived neurotrophic factor, synaptogenesis, learning and memory, motor learning, synaptic plasticity, microglial depletion, CX3CR1, diphtheria toxin receptor, neuroplasticity
- MeSH terms
- CX3C Chemokine Receptor 1, Animals, Learning, Neuronal Plasticity, Protein Kinases, Synapses, Signal Transduction, Gene Expression, Microglia, Brain-Derived Neurotrophic Factor, Receptors, Chemokine, Mice
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