New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective
Abstract
Microglia are the primary immune cells of the central nervous system. However, recent data indicate that microglia also contribute to diverse physiological and pathophysiological processes that extend beyond immune-related functions and there is a growing interest to understand the mechanisms through which microglia interact with other cells in the brain. In particular, the molecular processes that contribute to microglia-neuron communication in the healthy brain and their role in common brain diseases have been intensively studied during the last decade. In line with this, fate-mapping studies, genetic models and novel pharmacological approaches have revealed the origin of microglial progenitors, demonstrated the role of self-maintaining microglial populations during brain development or in adulthood, and identified the unexpectedly long lifespan of microglia that may profoundly change our view about senescence and age-related human diseases. Despite the exponentially increasing knowledge about microglia, the role of these cells in health and disease is still extremely controversial and the precise molecular targets for intervention are not well defined. This is in part due to the lack of microglia-specific manipulation approaches until very recently and to the high level of complexity of the interactions between microglia and other cells in the brain that occur at different temporal and spatial scales. In this review, we briefly summarize the known physiological roles of microglia-neuron interactions in brain homeostasis and attempt to outline some major directions and challenges of future microglia research.
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Animal models are largely inaccessible to real-time imaging and timely microglia manipulation.
“However, animal models are largely inaccessible to real-time imaging and timely microglia manipulation.15”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [15]
The “Challenges and future directions of microglia research” section calls for models that can selectively induce or inhibit microglial activation in real time, supporting a limitation in timely manipulation. But the same section describes in vivo two-photon imaging techniques as widely used, so it does not support the claim that animal models are largely inaccessible to real-time imaging. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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Cites
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · 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
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 · see citing works
ATP 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
A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Schulz, C., Perdiguero, E. G., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E. W., Pollard, J. W., et al. (2012) · Science · doi:10.1126/science.1219179 · Cited by 2,578 · see citing works
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543 · see citing works
Glial and neuronal control of brain blood flow
Attwell, D., Buchan, A. M., Charpak, S., Lauritzen, M., MacVicar, B. A., & Newman, E. A. (2010) · Nature · doi:10.1038/nature09613 · Cited by 2,511 · 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
How neuroinflammation contributes to neurodegeneration
Ransohoff, R. M. (2016) · Science · doi:10.1126/science.aag2590 · Cited by 1,967 · 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
Microglia Shape Adult Hippocampal Neurogenesis through Apoptosis-Coupled Phagocytosis
Sierra, A., Encinas, J. M., Deudero, J. J. P., Chancey, J. H., Enikolopov, G., Overstreet-Wadiche, L. S., Tsirka, S. E., & Maletic-Savatic, M. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.014 · Cited by 1,622 · 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
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
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
Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways
Kierdorf, K., Erny, D., Goldmann, T., Sander, V., Schulz, C., Perdiguero, E. G., Wieghofer, P., Heinrich, A., Riemke, P., Hölscher, C., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3318 · Cited by 1,457 · 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 · see citing works
Dai, X.-M., Ryan, G. R., Hapel, A. J., Dominguez, M. G., Russell, R. G., Kapp, S., Sylvestre, V., & Stanley, E. R. (2002) · Blood · doi:10.1182/blood.v99.1.111 · Cited by 1,184 · see citing works
Microglia: new roles for the synaptic stripper
Kettenmann, H., Kirchhoff, F., & Verkhratsky, A. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.023 · Cited by 1,173 · see citing works
Lauber, K., Bohn, E., Kröber, S. M., Xiao, Y.-J., Blumenthal, S. G., Lindemann, R. K., Marini, P., Wiedig, C., Zobywalski, A., Baksh, S., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00422-7 · Cited by 967 · see citing works
Layer V cortical neurons require microglial support for survival during postnatal development
Ueno, M., Fujita, Y., Tanaka, T., Nakamura, Y., Kikuta, J., Ishii, M., & Yamashita, T. (2013) · Nature Neuroscience · doi:10.1038/nn.3358 · Cited by 781 · see citing works
Spangenberg, E. E., Lee, R. J., Najafi, A. R., Rice, R. A., Elmore, M. R. P., Blurton-Jones, M., West, B. L., & Green, K. N. (2016) · Brain · doi:10.1093/brain/aww016 · Cited by 695 · see citing works
Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., & Pollard, J. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026317 · Cited by 649 · see citing works
Greter, M., Lelios, I., Pelczar, P., Hoeffel, G., Price, J., Leboeuf, M., Kündig, T. M., Frei, K., Ginhoux, F., Merad, M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.11.001 · Cited by 630 · 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
Self-citationHuang, 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
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
Olmos-Alonso, A., Schetters, S. T. T., Sri, S., Askew, K., Mancuso, R., Vargas-Caballero, M., Holscher, C., Perry, V. H., & Gomez-Nicola, D. (2016) · Brain · doi:10.1093/brain/awv379 · Cited by 532 · 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
A transcriptomic atlas of aged human microglia
Olah, M., Patrick, E., Villani, A.-C., Xu, J., White, C. C., Ryan, K. J., Piehowski, P., Kapasi, A., Nejad, P., Cimpean, M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-02926-5 · Cited by 482 · see citing works
Madry, C., Kyrargyri, V., Arancibia-Cárcamo, I. L., Jolivet, R., Kohsaka, S., Bryan, R. M., & Attwell, D. (2018) · Neuron · doi:10.1016/j.neuron.2017.12.002 · Cited by 464 · 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
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
Tanaka, T., Saito, H., & Matsuki, N. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-09-02959.1997 · Cited by 385 · see citing works
Hoshiko, M., Arnoux, I., Avignone, E., Yamamoto, N., & Audinat, E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1167-12.2012 · Cited by 384 · see citing works
Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain
Chen, Z., Jalabi, W., Hu, W., Park, H.-J., Gale, J. T., Kidd, G. J., Bernatowicz, R., Gossman, Z. C., Chen, J. T., Dutta, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms5486 · Cited by 319 · see citing works
Rice, 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
Elimination of microglia improves cognitive function following cranial irradiation
Acharya, M. M., Green, K. N., Allen, B. D., Najafi, A. R., Syage, A., Minasyan, H., Le, M. T., Kawashita, T., Giedzinski, E., Parihar, V. K., et al. (2016) · Scientific Reports · doi:10.1038/srep31545 · Cited by 259 · see citing works
Mrdjen, D., Pavlovic, A., Hartmann, F. J., Schreiner, B., Utz, S. G., Leung, B. P., Lelios, I., Heppner, F. L., Kipnis, J., Merkler, D., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.02.014 · Cited by 220 · see citing works
Kozai, T. D. Y., Vazquez, A. L., Weaver, C. L., Kim, S.-G., & Cui, X. T. (2012) · Journal of Neural Engineering · doi:10.1088/1741-2560/9/6/066001 · Cited by 215 · see citing works
The role of microglial P2X7: modulation of cell death and cytokine release
He, Y., Taylor, N., Fourgeaud, L., & Bhattacharya, A. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0904-8 · Cited by 194 · see citing works
Nikodemova, M., Kimyon, R. S., De, I., Small, A. L., Collier, L. S., & Watters, J. J. (2015) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.11.018 · Cited by 192 · see citing works
Microglia regulate hippocampal neurogenesis during chronic neurodegeneration
De Lucia, C., Rinchon, A., Olmos-Alonso, A., Riecken, K., Fehse, B., Boche, D., Perry, V. H., & Gomez-Nicola, D. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.11.001 · Cited by 110 · see citing works
Glia:Neuron index: Review and hypothesis to account for different values in various mammals.
Reichenbach, A. (1989) · Glia · doi:10.1002/glia.440020202 · Cited by 97 · see citing works
Cantaut-Belarif, Y., Antri, M., Pizzarelli, R., Colasse, S., Vaccari, I., Soares, S., Renner, M., Dallel, R., Triller, A., & Bessis, A. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201607048 · Cited by 56 · see citing works
Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain
Santoro, A., Spinelli, C. C., Martucciello, S., Nori, S. L., Capunzo, M., Puca, A. A., & Ciaglia, E. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0118-003r · Cited by 50 · see citing works
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Research works printed but not linked: 2
- Farzanehfar P (2018) Comparative review of adult midbrain and striatum neurogenesis with classical neurogenesis. Neurosci Res.
- Mallard C, Tremblay M-E, Vexler ZS (2018) Microglia and neonatal brain injury. Neuroscience Available at: http://linkinghub.elsevier.com/retrieve/pii/S0306452218300393.
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Bright, F., Werry, E. L., Dobson-Stone, C., Piguet, O., Ittner, L. M., Halliday, G. M., Hodges, J. R., Kiernan, M. C., Loy, C. T., Kassiou, M., et al. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0231-z · Cited by 280 · see citing works
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Kiss, T., Nyúl-Tóth, Á., DelFavero, J., Balasubramanian, P., Tarantini, S., Faakye, J., Gulej, R., Ahire, C., Ungvari, A., Yabluchanskiy, A., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00521-7 · Cited by 66 · see citing works
- Authors
- Pósfai, B., Cserép, C., Orsolits, B., & Dénes, Á.
- Affiliations
- Semmelweis University (HU)
- HUN-REN Institute of Experimental Medicine (HU)
- Corresponding author
- Dénes, Ádám
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 405
- Pages
- 103-117
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2803508229
- Cited by
- 98
- References
- 45
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 18 · 2023: 10 · 2022: 18 · 2021: 15 · 2020: 13 · 2019: 11 · 2018: 4
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Funders
- Hungarian Academy of Sciences (LP2016-4/2016)
- ERC-CoG (724994)
- 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, microglia-neuron interaction, microglial origin, microglial senescence, brain homeostasis, neuroinflammation, neurodegenerative diseases, brain development
- MeSH terms
- Animals, Brain, Brain Diseases, Cell Communication, Homeostasis, Humans, Neurons, Synapses, Microglia
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