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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Disease relevance of Microglia

  • Globoid cell leukodystrophy (GLD) is a severe genetic demyelinating disorder with an increased number of Ia (immune response antigen) positive brain microglia/macrophages [1].
  • Neurotactin messenger RNA is predominantly expressed in normal murine brain and its protein expression in activated brain microglia is upregulated in mice with experimental autoimmune encephalomyelitis, as well as in mice treated with lipopolysaccharide [2].
  • Recent evidence indicates that activated microglia are key cellular intermediaries in the pathogenesis of nerve injury-induced pain hypersensitivity because P2X(4) purinoceptors and p38 mitogen-activated protein kinase, which are present in activated microglia, are required molecular mediators [3].
  • Minocycline treatment for 4 days resulted in a 70% reduction in mRNA induction of interleukin-1beta-converting enzyme, a caspase that is induced in microglia after ischemia [4].
  • The treatment inhibits morphological activation of microglia in the area adjacent to the infarction, inhibits induction of IL-1beta-converting enzyme, and reduces cyclooxygenase-2 expression and prostaglandin E(2) production [5].

Psychiatry related information on Microglia


High impact information on Microglia

  • To determine the exact position of a gene affecting expression of MHC molecules, we finely mapped a previously defined rat quantitative trait locus regulating MHC class II on microglia in an advanced intercross line [11].
  • The reduction of parenchymal plaques in hAPP/TGF-beta1 mice was associated with a strong activation of microglia and an increase in inflammatory mediators [12].
  • Activation of brain microglia by peripheral immune challenges elicited neurodegeneration in hCD4 mice but not in nontransgenic controls [13].
  • Role of microglia and host prion protein in neurotoxicity of a prion protein fragment [14].
  • Mononuclear phagocytes, including microglia, express scavenger receptors that mediate endocytosis of oxidized low-density lipoproteins, and adhesion to glucose-modified extra-cellular matrix proteins [15].

Chemical compound and disease context of Microglia


Biological context of Microglia


Anatomical context of Microglia


Associations of Microglia with chemical compounds


Gene context of Microglia

  • Although EPO is clearly antiapoptotic for neurons after experimental stroke, it is unknown whether EPO also directly modulates EPO receptor (EPO-R)-expressing glia, microglia, and other inflammatory cells [36].
  • CCR5, a RANTES receptor, was detected on lymphocytic cells, macrophages, and microglia in actively demyelinating MS brain lesions [37].
  • In contrast, TKP or depletion of macrophages/microglia did not prevent SDF-1 neurotoxicity [38].
  • Finally, we report that genetic ablation of ERalpha is associated with a spontaneous reactive phenotype of microglia in specific brain regions of adult ERalpha-null mice [39].
  • Microglia proliferate, and astrocytes upregulate GFAP along central axons undergoing anterograde, Wallerian, degeneration [40].

Analytical, diagnostic and therapeutic context of Microglia


  1. Absence of MHC class II molecules reduces CNS demyelination, microglial/macrophage infiltration, and twitching in murine globoid cell leukodystrophy. Matsushima, G.K., Taniike, M., Glimcher, L.H., Grusby, M.J., Frelinger, J.A., Suzuki, K., Ting, J.P. Cell (1994) [Pubmed]
  2. Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation. Pan, Y., Lloyd, C., Zhou, H., Dolich, S., Deeds, J., Gonzalo, J.A., Vath, J., Gosselin, M., Ma, J., Dussault, B., Woolf, E., Alperin, G., Culpepper, J., Gutierrez-Ramos, J.C., Gearing, D. Nature (1997) [Pubmed]
  3. Neuropathic pain and spinal microglia: a big problem from molecules in "small" glia. Tsuda, M., Inoue, K., Salter, M.W. Trends Neurosci. (2005) [Pubmed]
  4. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Yrjänheikki, J., Keinänen, R., Pellikka, M., Hökfelt, T., Koistinaho, J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Yrjänheikki, J., Tikka, T., Keinänen, R., Goldsteins, G., Chan, P.H., Koistinaho, J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  6. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Yan, S.D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., Migheli, A., Nawroth, P., Stern, D., Schmidt, A.M. Nature (1996) [Pubmed]
  7. Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease. Baker, C.A., Manuelidis, L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Release of calcium from inositol 1,4,5-trisphosphate receptor-regulated stores by HIV-1 Tat regulates TNF-alpha production in human macrophages. Mayne, M., Holden, C.P., Nath, A., Geiger, J.D. J. Immunol. (2000) [Pubmed]
  9. Myelin basic protein-primed T cells of female but not male mice induce nitric-oxide synthase and proinflammatory cytokines in microglia: implications for gender bias in multiple sclerosis. Dasgupta, S., Jana, M., Liu, X., Pahan, K. J. Biol. Chem. (2005) [Pubmed]
  10. Peripheral benzodiazepine receptor ligand PK11195 reduces microglial activation and neuronal death in quinolinic acid-injected rat striatum. Ryu, J.K., Choi, H.B., McLarnon, J.G. Neurobiol. Dis. (2005) [Pubmed]
  11. MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction. Swanberg, M., Lidman, O., Padyukov, L., Eriksson, P., Akesson, E., Jagodic, M., Lobell, A., Khademi, M., Börjesson, O., Lindgren, C.M., Lundman, P., Brookes, A.J., Kere, J., Luthman, H., Alfredsson, L., Hillert, J., Klareskog, L., Hamsten, A., Piehl, F., Olsson, T. Nat. Genet. (2005) [Pubmed]
  12. TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Wyss-Coray, T., Lin, C., Yan, F., Yu, G.Q., Rohde, M., McConlogue, L., Masliah, E., Mucke, L. Nat. Med. (2001) [Pubmed]
  13. Novel role of human CD4 molecule identified in neurodegeneration. Buttini, M., Westland, C.E., Masliah, E., Yafeh, A.M., Wyss-Coray, T., Mucke, L. Nat. Med. (1998) [Pubmed]
  14. Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. Brown, D.R., Schmidt, B., Kretzschmar, H.A. Nature (1996) [Pubmed]
  15. Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils. El Khoury, J., Hickman, S.E., Thomas, C.A., Cao, L., Silverstein, S.C., Loike, J.D. Nature (1996) [Pubmed]
  16. HIV interactions with cells of the nervous system. Dubois-Dalcq, M., Altmeyer, R., Chiron, M., Wilt, S. Curr. Opin. Neurobiol. (1995) [Pubmed]
  17. Interleukin-1beta promotes oligodendrocyte death through glutamate excitotoxicity. Takahashi, J.L., Giuliani, F., Power, C., Imai, Y., Yong, V.W. Ann. Neurol. (2003) [Pubmed]
  18. Mechanisms underlying neuronal death induced by chromogranin A-activated microglia. Ciesielski-Treska, J., Ulrich, G., Chasserot-Golaz, S., Zwiller, J., Revel, M.O., Aunis, D., Bader, M.F. J. Biol. Chem. (2001) [Pubmed]
  19. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Banati, R.B., Newcombe, J., Gunn, R.N., Cagnin, A., Turkheimer, F., Heppner, F., Price, G., Wegner, F., Giovannoni, G., Miller, D.H., Perkin, G.D., Smith, T., Hewson, A.K., Bydder, G., Kreutzberg, G.W., Jones, T., Cuzner, M.L., Myers, R. Brain (2000) [Pubmed]
  20. Oligodendrocytes and microglia are selectively vulnerable to combined hypoxia and hypoglycemia injury in vitro. Lyons, S.A., Kettenmann, H. J. Cereb. Blood Flow Metab. (1998) [Pubmed]
  21. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Hoek, R.M., Ruuls, S.R., Murphy, C.A., Wright, G.J., Goddard, R., Zurawski, S.M., Blom, B., Homola, M.E., Streit, W.J., Brown, M.H., Barclay, A.N., Sedgwick, J.D. Science (2000) [Pubmed]
  22. Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis. Walsh, M.J., Murray, J.M. J. Clin. Invest. (1998) [Pubmed]
  23. In-vivo measurement of activated microglia in dementia. Cagnin, A., Brooks, D.J., Kennedy, A.M., Gunn, R.N., Myers, R., Turkheimer, F.E., Jones, T., Banati, R.B. Lancet (2001) [Pubmed]
  24. Identification of a molecular target of psychosine and its role in globoid cell formation. Im, D.S., Heise, C.E., Nguyen, T., O'Dowd, B.F., Lynch, K.R. J. Cell Biol. (2001) [Pubmed]
  25. Modified amino acid copolymers suppress myelin basic protein 85-99-induced encephalomyelitis in humanized mice through different effects on T cells. Illés, Z., Stern, J.N., Reddy, J., Waldner, H., Mycko, M.P., Brosnan, C.F., Ellmerich, S., Altmann, D.M., Santambrogio, L., Strominger, J.L., Kuchroo, V.K. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  26. Synthesis of nitric oxide in CNS glial cells. Murphy, S., Simmons, M.L., Agullo, L., Garcia, A., Feinstein, D.L., Galea, E., Reis, D.J., Minc-Golomb, D., Schwartz, J.P. Trends Neurosci. (1993) [Pubmed]
  27. Multiple sclerosis: Fas signaling in oligodendrocyte cell death. D'Souza, S.D., Bonetti, B., Balasingam, V., Cashman, N.R., Barker, P.A., Troutt, A.B., Raine, C.S., Antel, J.P. J. Exp. Med. (1996) [Pubmed]
  28. Abeta-induced meningoencephalitis is IFN-gamma-dependent and is associated with T cell-dependent clearance of Abeta in a mouse model of Alzheimer's disease. Monsonego, A., Imitola, J., Petrovic, S., Zota, V., Nemirovsky, A., Baron, R., Fisher, Y., Owens, T., Weiner, H.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  29. Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of inducible nitric-oxide synthase by 15-deoxy-Delta12,14-prostaglandin J2. Petrova, T.V., Akama, K.T., Van Eldik, L.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  30. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Abbadie, C., Lindia, J.A., Cumiskey, A.M., Peterson, L.B., Mudgett, J.S., Bayne, E.K., DeMartino, J.A., MacIntyre, D.E., Forrest, M.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  31. Differential tumor necrosis factor alpha expression by astrocytes from experimental allergic encephalomyelitis-susceptible and -resistant rat strains. Chung, I.Y., Norris, J.G., Benveniste, E.N. J. Exp. Med. (1991) [Pubmed]
  32. Role of p75 neurotrophin receptor in the neurotoxicity by beta-amyloid peptides and synergistic effect of inflammatory cytokines. Perini, G., Della-Bianca, V., Politi, V., Della Valle, G., Dal-Pra, I., Rossi, F., Armato, U. J. Exp. Med. (2002) [Pubmed]
  33. CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Bezzi, P., Domercq, M., Brambilla, L., Galli, R., Schols, D., De Clercq, E., Vescovi, A., Bagetta, G., Kollias, G., Meldolesi, J., Volterra, A. Nat. Neurosci. (2001) [Pubmed]
  34. Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice. Zhang, L., Nair, A., Krady, K., Corpe, C., Bonneau, R.H., Simpson, I.A., Vannucci, S.J. J. Clin. Invest. (2004) [Pubmed]
  35. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. Pahan, K., Sheikh, F.G., Namboodiri, A.M., Singh, I. J. Clin. Invest. (1997) [Pubmed]
  36. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. Villa, P., Bigini, P., Mennini, T., Agnello, D., Laragione, T., Cagnotto, A., Viviani, B., Marinovich, M., Cerami, A., Coleman, T.R., Brines, M., Ghezzi, P. J. Exp. Med. (2003) [Pubmed]
  37. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. Sørensen, T.L., Tani, M., Jensen, J., Pierce, V., Lucchinetti, C., Folcik, V.A., Qin, S., Rottman, J., Sellebjerg, F., Strieter, R.M., Frederiksen, J.L., Ransohoff, R.M. J. Clin. Invest. (1999) [Pubmed]
  38. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Kaul, M., Lipton, S.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  39. Estrogen receptor-alpha mediates the brain antiinflammatory activity of estradiol. Vegeto, E., Belcredito, S., Etteri, S., Ghisletti, S., Brusadelli, A., Meda, C., Krust, A., Dupont, S., Ciana, P., Chambon, P., Maggi, A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  40. Central neuron-glial and glial-glial interactions following axon injury. Aldskogius, H., Kozlova, E.N. Prog. Neurobiol. (1998) [Pubmed]
  41. Transforming growth factor-betas in neurodegenerative disease. Flanders, K.C., Ren, R.F., Lippa, C.F. Prog. Neurobiol. (1998) [Pubmed]
  42. LPS induces CD40 gene expression through the activation of NF-kappaB and STAT-1alpha in macrophages and microglia. Qin, H., Wilson, C.A., Lee, S.J., Zhao, X., Benveniste, E.N. Blood (2005) [Pubmed]
  43. Upregulation of a new microglial gene, mrf-1, in response to programmed neuronal cell death and degeneration. Tanaka, S., Suzuki, K., Watanabe, M., Matsuda, A., Tone, S., Koike, T. J. Neurosci. (1998) [Pubmed]
  44. Predominant expression of platelet-activating factor receptor in the rat brain microglia. Mori, M., Aihara, M., Kume, K., Hamanoue, M., Kohsaka, S., Shimizu, T. J. Neurosci. (1996) [Pubmed]
  45. Tenascin-R is antiadhesive for activated microglia that induce downregulation of the protein after peripheral nerve injury: a new role in neuronal protection. Angelov, D.N., Walther, M., Streppel, M., Guntinas-Lichius, O., Neiss, W.F., Probstmeier, R., Pesheva, P. J. Neurosci. (1998) [Pubmed]
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