Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-27T06:22:21.189Z Has data issue: false hasContentIssue false
  • English
  • Français

Functions of microglia in the central nervous system – beyond the immune response

Published online by Cambridge University Press:  22 May 2012

Hiroaki Wake ,
Andrew J. Moorhouse  and
Junichi Nabekura
Hiroaki Wake*
Affiliation:
Nervous System Development and Plasticity Section, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD, USA
Andrew J. Moorhouse
Affiliation:
School of Medical Sciences, The University of New South Wales, Sydney, Australia
Junichi Nabekura
Affiliation:
Division of Homeostatic Development, National Institute of Physiological Sciences, Okazaki, Japan Department of Physiological Sciences, The Graduate University for Advanced Studies, Hayama, Japan
*
Correspondence should be addressed to: Hiroaki Wake, Nervous Systems Development and Plasticity Section, National Institutes of Health, NICHD, Building 35, Room 2A213, 35 Lincoln Drive, Bethesda, MD 20892, USA phone: (301) 451-4078 email: wakeh@mail.nih.gov
Get access Rights & Permissions [Opens in a new window]

Abstract

Microglia cells are the immune cells of the central nervous system and consequently play important roles in brain infections and inflammation. Recent in vivo imaging studies have revealed that in the resting healthy brain, microglia are highly dynamic, moving constantly to actively survey the brain parenchyma. These active microglia can rapidly respond to pathological insults, becoming activated to induce a range of effects that may contribute to both pathogenesis, or to confer neuronal protection. However, interactions between microglia and neurons are being recognized as important in shaping neural circuit activity under more normal, physiological conditions. During development and neurogenesis, microglia interactions with neurons help to shape the final patterns of neural circuits important for behavior and with implications for diseases. In the mature brain, microglia can respond to changes in sensory activity and can influence neuronal activity acutely and over the long term. Microglia seem to be particularly involved in monitoring the integrity of synaptic function. In this review, we discuss some of these new insights into the involvement of microglia in neural circuits.

Keywords

Microgliasynapsesynapse stripping
Type
Research Article
Information
Neuron Glia Biology , Volume 7 , Special Issue 1: The Physiological Function of Microglia , February 2011 , pp. 47 - 53
Copyright
Copyright © Cambridge University Press 2012. This is a work of the U.S. Government and is not subject to copyright protection in the United States.

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Ashwell, K. (1990) Microglia and cell death in the developing mouse cerebellum. Brain Research. Developmental Brain Research 55, 219–230.CrossRefGoogle ScholarPubMed
Bessis, A., Bechade, C., Bernard, D. and Roumier, A. (2007) Microglial control of neuronal death and synaptic properties. Glia 55, 233–238.CrossRefGoogle ScholarPubMed
Biber, K., Neumann, H., Inoue, K. and Boddeke, H.W. (2007) Neuronal ‘On’ and ‘Off’ signals control microglia. Trends in Neurosciences 30, 596–602.CrossRefGoogle ScholarPubMed
Blinzinger, K. and Kreutzberg, G. (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Zeitschrift fur Zellforschung und mikroskopische Anatomie 85, 145–157.CrossRefGoogle ScholarPubMed
Chan, W.Y., Kohsaka, S. and Rezaie, P. (2007) The origin and cell lineage of microglia: new concepts. Brain Research Reviews 53, 344–354.CrossRefGoogle ScholarPubMed
Choi, S.H., Veeraraghavalu, K., Lazarov, O., Marler, S., Ransohoff, R.M., Ramirez, J.M. et al. (2008) Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron 59, 568–580.CrossRefGoogle ScholarPubMed
Chu, Y., Jin, X., Parada, I., Pesic, A., Stevens, B., Barres, B. et al. (2010) Enhanced synaptic connectivity and epilepsy in C1q knockout mice. Proceedings of the National Academy of Sciences of the U.S.A. 107, 7975–7980.CrossRefGoogle ScholarPubMed
Coull, J.A., Beggs, S., Boudreau, D., Boivin, D., Tsuda, M., Inoue, K. et al. (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438, 1017–1021.CrossRefGoogle ScholarPubMed
Cuadros, M.A. and Navascues, J. (1998) The origin and differentiation of microglial cells during development. Progress in Neurobiology 56, 173–189.CrossRefGoogle ScholarPubMed
Cullheim, S. and Thams, S. (2007) The microglial networks of the brain and their role in neuronal network plasticity after lesion. Brain Research Reviews 55, 89–96.CrossRefGoogle ScholarPubMed
Curtis, M.A., Faull, R.L. and Eriksson, P.S. (2007) The effect of neurodegenerative diseases on the subventricular zone. Nature Reviews. Neuroscience 8, 712–723.CrossRefGoogle ScholarPubMed
Davalos, D., Grutzendler, J., Yang, G., Kim, J.V., Zuo, Y., Jung, S. et al. (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 8, 752–758.CrossRefGoogle ScholarPubMed
Denk, W., Strickler, J.H. and Webb, W.W. (1990) Two-photon laser scanning fluorescence microscopy. Science 248, 73–76.CrossRefGoogle ScholarPubMed
Finsen, B.R., Jorgensen, M.B., Diemer, N.H. and Zimmer, J. (1993) Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus. Glia 7, 41–49.CrossRefGoogle ScholarPubMed
Frautschy, S.A., Walicke, P.A. and Baird, A. (1991) Localization of basic fibroblast growth factor and its mRNA after CNS injury. Brain Research 553, 291–299.CrossRefGoogle ScholarPubMed
Fuhrmann, M., Bittner, T., Jung, C.K., Burgold, S., Page, R.M., Mitteregger, G. et al. (2010) Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nature Neuroscience 13, 411–413.CrossRefGoogle Scholar
Jin, K., Minami, M., Lan, J.Q., Mao, X.O., Batteur, S., Simon, R.P. et al. (2001) Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proceedings of the National Academy of Sciences of the U.S.A. 98, 4710–4715.CrossRefGoogle ScholarPubMed
Kalla, R., Liu, Z., Xu, S., Koppius, A., Imai, Y., Kloss, C.U. et al. (2001) Microglia and the early phase of immune surveillance in the axotomized facial motor nucleus: impaired microglial activation and lymphocyte recruitment but no effect on neuronal survival or axonal regeneration in macrophage-colony stimulating factor-deficient mice. Journal of Comparative Neurology 436, 182–201.CrossRefGoogle ScholarPubMed
Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M. et al. (2007) UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446, 1091–1095.CrossRefGoogle ScholarPubMed
Koketsu, D., Furuichi, Y., Maeda, M., Matsuoka, N., Miyamoto, Y. and Hisatsune, T. (2006) Increased number of new neurons in the olfactory bulb and hippocampus of adult non-human primates after focal ischemia. Experimental Neurology 199, 92–102.CrossRefGoogle ScholarPubMed
Kuruba, R., Hattiangady, B. and Shetty, A.K. (2009) Hippocampal neurogenesis and neural stem cells in temporal lobe epilepsy. Epilepsy and Behavior 14 (Suppl. 1), 65–73.CrossRefGoogle ScholarPubMed
Lambertsen, K.L., Clausen, B.H., Babcock, A.A., Gregersen, R., Fenger, C., Nielsen, H.H. et al. (2009) Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. Journal of Neuroscience 29, 1319–1330.CrossRefGoogle ScholarPubMed
Lavin, M.F., Gueven, N., Bottle, S. and Gatti, R.A. (2007) Current and potential therapeutic strategies for the treatment of ataxia-telangiectasia. British Medical Bulletin 81–82, 129–147.CrossRefGoogle ScholarPubMed
Liu, Z., Condello, C., Schain, A., Harb, R. and Grutzendler, J. (2010) CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar amyloid-beta phagocytosis. Journal of Neuroscience 30, 17091–17101.CrossRefGoogle ScholarPubMed
Maezawa, I. and Jin, L.W. (2010) Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. Journal of Neuroscience 30, 5346–5356.CrossRefGoogle ScholarPubMed
Marin-Teva, J.L., Cuadros, M.A., Calvente, R., Almendros, A. and Navascues, J. (1999) Naturally occurring cell death and migration of microglial precursors in the quail retina during normal development. Journal of Comparative Neurology 412, 255–275.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Marin-Teva, J.L., Dusart, I., Colin, C., Gervais, A., van Rooijen, N. and Mallat, M. (2004) Microglia promote the death of developing Purkinje cells. Neuron 41, 535–547.CrossRefGoogle ScholarPubMed
Mattocks, M. and Tropepe, V. (2010) Waste management and adult neurogenesis. Cell Stem Cell 7, 421–422.CrossRefGoogle ScholarPubMed
Merrill, J.E. (1992) Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain development: normal and pathological. Developmental Neuroscience 14, 1–10.CrossRefGoogle ScholarPubMed
Neniskyte, U., Neher, J.J. and Brown, G.C. (2011) Neuronal death induced by nanomolar amyloid beta is mediated by primary phagocytosis of neurons by microglia. Journal of Biological Chemistry 286, 39904–39913.CrossRefGoogle ScholarPubMed
Nimmerjahn, A., Kirchhoff, F. and Helmchen, F. (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314–1318.CrossRefGoogle ScholarPubMed
Noda, M., Nakanishi, H., Nabekura, J. and Akaike, N. (2000) AMPA-kainate subtypes of glutamate receptor in rat cerebral microglia. Journal of Neuroscience 20, 251–258.CrossRefGoogle ScholarPubMed
Paolicelli, R.C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P. et al. (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333, 1456–1458.CrossRefGoogle ScholarPubMed
Parent, J.M. (2002) The role of seizure-induced neurogenesis in epileptogenesis and brain repair. Epilepsy Research 50, 179–189.CrossRefGoogle ScholarPubMed
Parent, J.M., Valentin, V.V. and Lowenstein, D.H. (2002) Prolonged seizures increase proliferating neuroblasts in the adult rat subventricular zone-olfactory bulb pathway. Journal of Neuroscience 22, 3174–3188.CrossRefGoogle ScholarPubMed
Pascual, O., Ben Achour, S., Rostaing, P., Triller, A. and Bessis, A. (2012) Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proceedings of the National Academy of Sciences of the U.S.A. 109, E197–E205.CrossRefGoogle ScholarPubMed
Rakic, S. and Zecevic, N. (2000) Programmed cell death in the developing human telencephalon. European Journal of Neuroscience 12, 2721–2734.CrossRefGoogle ScholarPubMed
Ransohoff, R.M. and Perry, V.H. (2009) Microglial physiology: unique stimuli, specialized responses. Annual Review of Immunology 27, 119–145.CrossRefGoogle ScholarPubMed
Rio-Hortega, P. del. (1920) La microglia y su transformacion en celulas en bastoncito y cuerpos granulo-adiposos. Archivos de Neurobiologia. also, Trabajos del Laboratorio de Investigaciones biologicas xviii, 37–83.Google Scholar
Rio-Hortega, P. del. (1921a) Estudios sobre la neuroglia. La glia de escasas radiaciones (oligodendroglia). Boletin de la Real Sociedad Espafaola de Historia Natural 21, 64–92.Google Scholar
Rio-Hortega, P. del. (1921b) El “tercer elemento” de los centros nerviosos. Histogenesis y evolucion normal; Exodo y distribucion regional de la microglia. Memorias de la Real Soiedad Espanola de Historia Natural 11, 213–268.Google Scholar
Rodriguez, J.J., Jones, V.C. and Verkhratsky, A. (2009) Impaired cell proliferation in the subventricular zone in an Alzheimer's disease model. Neuroreport 20, 907–912.CrossRefGoogle Scholar
Rogers, J.T., Morganti, J.M., Bachstetter, A.D., Hudson, C.E., Peters, M.M., Grimmig, B.A. et al. (2011) CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. Journal of Neuroscience 31, 16241–16250.CrossRefGoogle ScholarPubMed
Saha, R.N., Ghosh, A., Palencia, C.A., Fung, Y.K., Dudek, S.M. and Pahan, K. (2009) TNF-alpha preconditioning protects neurons via neuron-specific up-regulation of CREB-binding protein. Journal of Immunology 183, 2068–2078.CrossRefGoogle ScholarPubMed
Sawada, M., Kondo, N., Suzumura, A. and Marunouchi, T. (1989) Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Research 491, 394–397.CrossRefGoogle ScholarPubMed
Schwartz, M. and Shechter, R. (2010) Systemic inflammatory cells fight off neurodegenerative disease. Nature Reviews. Neurology 6, 405–410.CrossRefGoogle ScholarPubMed
Sierra, A., Encinas, J.M., Deudero, J.J., Chancey, J.H., Enikolopov, G., Overstreet-Wadiche, L.S. et al. (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7, 483–495.CrossRefGoogle ScholarPubMed
Stevens, B., Allen, N.J., Vazquez, L.E., Howell, G.R., Christopherson, K.S., Nouri, N. et al. (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131, 1164–1178.CrossRefGoogle ScholarPubMed
Trapp, B.D., Wujek, J.R., Criste, G.A., Jalabi, W., Yin, X., Kidd, G.J. et al. (2007) Evidence for synaptic stripping by cortical microglia. Glia 55, 360–368.CrossRefGoogle ScholarPubMed
Tremblay, M.E., Lowery, R.L. and Majewska, A.K. (2010) Microglial interactions with synapses are modulated by visual experience. PLoS Biology 8, e1000527.CrossRefGoogle ScholarPubMed
Tsuda, M., Shigemoto-Mogami, Y., Koizumi, S., Mizokoshi, A., Kohsaka, S., Salter, M.W. et al. (2003) P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 424, 778–783.CrossRefGoogle ScholarPubMed
Wake, H., Moorhouse, A.J., Jinno, S., Kohsaka, S. and Nabekura, J. (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. Journal of Neuroscience 29, 3974–3980.CrossRefGoogle ScholarPubMed
Wakselman, S., Bechade, C., Roumier, A., Bernard, D., Triller, A. and Bessis, A. (2008) Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor. Journal of Neuroscience 28, 8138–8143.CrossRefGoogle ScholarPubMed
Wu, L.J. and Zhuo, M. (2008) Resting microglial motility is independent of synaptic plasticity in mammalian brain. Journal of Neurophysiology 99, 2026–2032.CrossRefGoogle ScholarPubMed
Ziv, Y., Ron, N., Butovsky, O., Landa, G., Sudai, E., Greenberg, N. et al. (2006) Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nature Neuroscience 9, 268–275.CrossRefGoogle Scholar