Fol. Biol. 2017, 63, 85-90

https://doi.org/10.14712/fb2017063030085

Microglia: Physiological Functions Revealed through Morphological Profiles

K. Cho1, Go-Eun Choi2

1Granduate School of International Studies, Dong-A University, Busan, Republic of Korea
2Institute of Convergence Bio-Health, Dong-A University, Busan, Republic of Korea

Received February 2017
Accepted March 2017

References

1. Ashwell, K. (1990) Microglia and cell death in the developing mouse cerebellum. Brain Res. Dev. Brain Res. 55, 219-230. <https://doi.org/10.1016/0165-3806(90)90203-B>
2. Berger, J. V., Deumens, R., Goursaud, S., Schafer, S., Lavand’homme, P., Joosten, E. A., Hermans, E. (2011) Enhanced neuroinflammation and pain hypersensitivity after peripheral nerve injury in rats expressing mutated superoxide dismutase 1. J. Neuroinflammation 8, 33. <https://doi.org/10.1186/1742-2094-8-33>
3. Bessis, A., Bechade, C., Bernard, D., Roumier, A. (2007) Microglial control of neuronal death and synaptic properties. Glia 55, 233-238. <https://doi.org/10.1002/glia.20459>
4. Chan, W. Y., Kohsaka, S., Rezaie, P. (2007). The origin and cell lineage of microglia – new concepts. Brain Res. Rev. 53, 344-354. <https://doi.org/10.1016/j.brainresrev.2006.11.002>
5. Charles, N. A., Holland, E. C., Gilbertson, R., Glass, R., Kettenmann, H. (2011) The brain tumor microenvironment. Glia 59, 1169-1180. <https://doi.org/10.1002/glia.21136>
6. Cherry, J. D., Olschowka, J. A., O’Banion, M. K. (2014) Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J. Neuroinflammation 11.
7. Desestret, V., Riou, A., Chauveau, F., Cho, T. H., Devillard, E., Marinescu, M., Ferrera, R., Rey, C., Chanal, M., Angoulvant, D., Honnorat, J., Nighoghossian, N., Berthezène, Y., Nataf, S., Wiart, M. (2013) In vitro and in vivo models of cerebral ischemia show discrepancy in therapeutic effects of M2 macrophages. PLoS One 8, e67063. <https://doi.org/10.1371/journal.pone.0067063>
8. Fairweather, D., Cihakova, D. (2009) Alternatively activated macrophages in infection and autoimmunity. J. Autoimmun. 33, 222-230. <https://doi.org/10.1016/j.jaut.2009.09.012>
9. Fleisher-Berkovich, S., Filipovich-Rimon, T., Ben-Shmuel, S., Hulsmann, C., Kummer, M. P., Heneka, M. T. (2010) Distinct modulation of microglial amyloid β phagocytosis and migration by neuropeptides. J. Neuroinflammation 7.
10. Fricker, M., Oliva-Martin, M. J., Brown, G. C. (2012) Primary phagocytosis of viable neurons by microglia activated with LPS or A β is dependent on calreticulin/LRP phagocytic signalling. J. Neuroinflammation 9.
11. Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., Samokhvalov, I. M., Merad, M. (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841-845. <https://doi.org/10.1126/science.1194637>
12. Gomez-Nicola, D., Perry, V. H. (2015) Microglial dynamics and role in the healthy and diseased brain: a paradigm of functional plasticity. Neuroscientist 21, 169-184. <https://doi.org/10.1177/1073858414530512>
13. Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S., Lupton, M. K., Ryten, M., Brown, K., Lowe, J., Ridge, P. G., Hammer, M. B., Wakutani, Y., Hazrati, L., Proitsi, P., Newhouse, S., Lohmann, E., Erginel-Unaltuna, N., Medway, C., Hanagasi, H., Troakes, C., Gurvit, H., Bilgic, B., Al-Sarraj, S., Benitez, B., Cooper, B., Carrell, D., Emre, M., Zou, F., Ma, L., Murray, M., Dickson, D., Younkin, S., Petersen, R. C., Corcoran, C. D., Cai, Y., Oliveira, C., Ribeiro, M. H., Santana, I., Tschanz, J. T., Gibbs, J., Norton, M. C., Kloszewska, I., Mecocci, P., Soininen, H., Tsolaki, M., Vellas, B., Munger, R. G., Mann, D. M., Pickering- Brown, S., Lovestone, S., Beck, J., Mead, S., Collinge, J., Parsons, L., Pocock, J., Morris, J. C., Revesz, T., Lashley, T., Fox, N. C., Rossor, M. N., Grenier-Boley, B., Bellenguez, C., Moskvina, V., Sims, R., Harold, D., Williams, J., Lambert, J. C., Amouyel, P., Graff-Radford, N., Goate, A., Rademakers, R., Morgan, K., Powell, J., St George-Hyslop, P., Singleton, A., Hardy, J., Gerrish, A., Chapman, J., Abraham, R., Hollingworth, P., Hamshere, M., Pahwa, J. S., Dowzell, K., Williams, A., Jones, N., Thomas, C., Stretton, A., Morgan, A., Williams, K., Thomas, S., Brayne, C., Rubinsztein, D. C., Gill, M., Lawlor, B., Lynch, A., Passmore, P., Craig, D., McGuinness, B., Johnston, J. A., Todd, S., Holmes, C., Smith, A., Love, S., Kehoe, P. G., Maier, W., Jessen, F., Heun, R., Kölsch, H., Schürmann, B., Ramirez, A., van den Bussche, H., Heuser, I., Kornhuber, J., Wiltfang, J., Dichgans, M., Frölich, L., Hampel, H., Hüll, M., Rujescu, D., Nowotny, P., Mayo, K., Livingston, G., Bass, N. J., Gurling, H., McQuillin, A., Gwilliam, R., Deloukas, P., Nöthen, M. M., Holmans, P., O’Donovan, M., Owen, M. J., Zelenika, D., Epelbaum, J., Dartigues, J. F., Tzourio, C., Berr, C., Boland, A., Campion, D., Alpérovitch, A., Lathrop, M., Smith, C., Trabzuni, D., Walker, R., Weale, M. (2013) TREM2 variants in Alzheimer’s disease. N. Engl. J. Med. 368, 117-127. <https://doi.org/10.1056/NEJMoa1211851>
14. Hanisch, U. K. (2002) Microglia as a source and target of cytokines. Glia 40, 140-155. <https://doi.org/10.1002/glia.10161>
15. Hanisch, U. K., Kettenmann, H. (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10, 1387-1394. <https://doi.org/10.1038/nn1997>
16. Holmans, P., Moskvina, V., Jones, L., Sharma, M., International Parkinson’s Disease Genomics Consortium, Vedernikov, A., Buchel, F., Saad, M., Bras, J. M., Bettella, F., Nicolaou, N., Simón-Sánchez, J., Mittag, F., Gibbs, J. R., Schulte, C., Durr, A., Guerreiro, R., Hernandez, D., Brice, A., Stefánsson, H., Majamaa, K., Gasser, T., Heutink, P., Wood, N. W., Martinez, M., Singleton, A. B., Nalls, M. A., Hardy, J., Morris, H. R., Williams, N. M., Arepalli, S., Barker, R., Barrett, J., Ben-Shlomo, Y., Berendse, H. W., Berg, D., Bhatia, K., de Bie, R. M., Biffi, A., Bloem, B., Brice, A., Bochdanovits, Z., Bonin, M., Bras, J. M., Brockmann, K., Brooks, J., Burn, D. J., Charlesworth, G., Chen, H., Chinnery, P. F., Chong, S., Clarke, C. E., Cookson, M. R., Cooper, J. M., Corvol, J. C., Counsell, C., Damier, P., Dartigues, J. F., Deloukas, P., Deuschl, G., Dexter, D. T., van Dijk, K. D., Dillman, A., Durif, F., Durr, A., Edkins, S., Evans, J. R., Foltynie, T., Gao, J., Gardner, M., Gasser, T., Gibbs, J. R., Goate, A., Gray, E., Guerreiro, R., Gústafsson, O., Hardy, J., Harris, C., Hernandez, D. G., Heutink, P., van Hilten, J. J., Hofman, A., Hollenbeck, A., Holmans, P., Holton, J., Hu, M., Huber, H., Hudson, G., Hunt, S. E., Huttenlocher, J., Illig, T., Langford, C., Lees, A., Lesage, S., Lichtner, P., Limousin, P., Lopez, G., Lorenz, D., Martinez, M., McNeill, A., Moorby, C., Moore, M., Morris, H., Morrison, K. E., Moskvina, V., Mudanohwo, E., Nalls, M. A,. Pearson, J., Perlmutter, J. S., Pétursson, H., Plagnol, V., Pollak, P., Post, B., Potter, S., Ravina, B., Revesz, T., Riess, O., Rivadeneira, F., Rizzu, P., Ryten, M., Saad, M., Sawcer, S., Schapira, A., Scheffer, H., Sharma, M., Shaw, K., Sheerin, U. M., Shoulson, I., Schulte, C., Sidransky, E., Simón-Sánchez, J., Singleton, A. B., Smith, C., Stefánsson, H., Stefánsson, K., Steinberg, S., Stockton, J. D., Sveinbjornsdottir, S., Talbot, K., Tanner, C. M., Tashakkori-Ghanbaria, A., Tison, F., Trabzuni, D., Traynor, B. J., Uitterlinden, A. G., Velseboer, D., Vidailhet, M., Walker, R., van de Warrenburg, B., Wickremaratchi, M., Williams, N., Williams- Gray, C. H., Winder-Rhodes, S., Wood, N. (2013) A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson’s disease. Hum. Mol. Genet. 22, 1039-1049. <https://doi.org/10.1093/hmg/dds492>
17. Hooper, C., Pocock, J. M. (2007) Chromogranin A activates diverse pathways mediating inducible nitric oxide expression and apoptosis in primary microglia. Neurosci. Lett. 413, 227-232. <https://doi.org/10.1016/j.neulet.2006.11.068>
18. Imamoto, K., Leblond, C. P. (1978) Radioautographic investigation of gliogenesis in the corpus callosum of young rats. II. Origin of microglial cells. J. Comp. Neurol. 180, 139-163. <https://doi.org/10.1002/cne.901800109>
19. Inoue, K., Ozaki, S., Shiga, T., Ito, K., Masuda, T., Okado, N., Iseda, T., Kawaguchi, S., Ogawa, M., Bae, S. C., Yamashita, N., Itohara, S., Kudo, N., Ito, Y. (2002) Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons. Nat. Neurosci. 5, 946-954. <https://doi.org/10.1038/nn925>
20. Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., Rujescu, D., Hampel, H., Giegling, I., Andreassen, O. A., Engedal, K., Ulstein, I., Djurovic, S., Ibrahim-Verbaas, C., Hofman, A., Ikram, M. A., van Duijn, C. M., Thorsteinsdottir, U., Kong, A., Stefansson, K. (2013) Variant of TREM2 associated with the risk of Alzheimer’s disease. N. Engl. J. Med. 368, 107-116. <https://doi.org/10.1056/NEJMoa1211103>
21. Kao, A. W., Eisenhut, R. J., Martens, L. H., Nakamura, A., Huang, A., Bagley, J. A., Zhou, P., de Luis, A., Neukomm, L. J., Cabello J, Farese R. V. Jr., Kenyon, C. (2011) A neurodegenerative disease mutation that accelerates the clearance of apoptotic cells. Proc. Natl. Acad. Sci. USA 108, 4441-4446. <https://doi.org/10.1073/pnas.1100650108>
22. Kaur, C., Wu, C. H., Wen, C. Y., Ling, E. A. (1994) The effects of subcutaneous injections of glucocorticoids on amoeboid microglia in postnatal rats. Arch. Histol. Cytol. 57, 449-459. <https://doi.org/10.1679/aohc.57.449>
23. Kaur, C., Ling, E. A. (2009) Periventricular white matter damage in the hypoxic neonatal brain: role of microglial cells. Prog. Neurobiol. 87, 264-280. <https://doi.org/10.1016/j.pneurobio.2009.01.003>
24. Kingham, P. J., Pocock, J. M. (2000) Microglial apoptosis induced by chromogranin A is mediated by mitochondrial depolarisation and the permeability transition but not by cytochrome c release. J. Neurochem. 74, 1452-1462. <https://doi.org/10.1046/j.1471-4159.2000.0741452.x>
25. Lawson, L. J., Perry, V. H., Gordon, S. (1992) Turnover of resident microglia in the normal adult mouse brain. Neuroscience 48, 405-415. <https://doi.org/10.1016/0306-4522(92)90500-2>
26. Mantovani, A., Sozzani, S., Locati, M., Schioppa, T., Saccani, A., Allavena, P., Sica, A. (2004) Infiltration of tumours by macrophages and dendritic cells: tumour-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Novartis Found. Symp. 256, 137-145. <https://doi.org/10.1002/0470856734.ch10>
27. Mari, C., Karabiyikoglu, M., Goris, M. L., Tait, J. F., Yenari, M. A., Blankenberg, F. G. (2004) Detection of focal hypoxic- ischemic injury and neuronal stress in a rodent model of unilateral MCA occlusion/reperfusion using radiolabeled annexin V. Eur. J. Nucl. Med. Mol. I 31, 733-739. <https://doi.org/10.1007/s00259-004-1473-5>
28. Martinez, F. O., Gordon, S., Locati, M., Mantovani, A. (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J. Immunol. 177, 7303-7311. <https://doi.org/10.4049/jimmunol.177.10.7303>
29. Melchior, B., Garcia, A. E., Hsiung, B. K., Lo, K. M., Doose, J. M., Thrash, J. C., Stalder, A. K., Staufenbiel, M., Neumann, H., Carson, M. J. (2010) Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer’s disease. ASN Neuro. 2, e00037. <https://doi.org/10.1042/AN20100010>
30. Michell-Robinson, M. A., Touil, H., Healy, L. M., Owen, D. R., Durafourt, B. A., Bar-Or, A., Antel, J. P., Moore, C. S. (2015) Roles of microglia in brain development, tissue maintenance and repair. Brain 138, 1138-1159. <https://doi.org/10.1093/brain/awv066>
31. Miron, V. E., Boyd, A., Zhao, J. W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J., ffrench-Constant, C. (2013) M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat. Neurosci. 16, 1211-1218. <https://doi.org/10.1038/nn.3469>
32. Nagata, K., Asano, T., Nozawa, Y., Inagaki, M. (2004) Biochemical and cell biological analyses of a mammalian septin complex. J. Biol. Chem. 279, 55895-55904. <https://doi.org/10.1074/jbc.M406153200>
33. Neher, J. J., Neniskyte, U., Zhao, J. W., Bal-Price, A., Tolkovsky, A. M., Brown, G. C. (2011) Inhibition of microglial phagocytosis is sufficient to prevent inflammatory neuronal death. J. Immunol. 186, 4973-4983. <https://doi.org/10.4049/jimmunol.1003600>
34. Nimmerjahn, A., Kirchhoff, F., Helmchen, F. (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314-1318. <https://doi.org/10.1126/science.1110647>
35. Ohgidani, M., Kato, T. A., Setoyama, D., Sagata, N., Hashimoto, R., Shigenobu, K., Yoshida, T., Hayakawa, K., Shimokawa, N., Miura, D., Utsumi, H., Kanba, S. (2014) Direct induction of ramified microglia-like cells from human monocytes: dynamic microglial dysfunction in Nasu- Hakola disease. Sci. Rep. 4, 4957. <https://doi.org/10.1038/srep04957>
36. Perez-Pouchoulen, M., VanRyzin, J. W., McCarthy, M. M. (2015) Morphological and phagocytic profile of microglia in the developing rat cerebellum(1,2,3). eNeuro. 2, ENEURO.0036-15.2015. <https://doi.org/10.1523/ENEURO.0036-15.2015>
37. Ransohoff, R. M., Perry, V. H. (2009) Microglial physiology: unique stimuli, specialized responses. Annu. Rev. Immunol. 27, 119-145. <https://doi.org/10.1146/annurev.immunol.021908.132528>
38. Saijo, K., Glass, C. K. (2011) Microglial cell origin and phenotypes in health and disease. Nat. Rev. Immunol. 11, 775-787. <https://doi.org/10.1038/nri3086>
39. Sanagi, T., Yuasa, S., Nakamura, Y., Suzuki, E., Aoki, M., Warita, H., Itoyama, Y., Uchino, S., Kohsaka, S., Ohsawa, K. (2010) Appearance of phagocytic microglia adjacent to motoneurons in spinal cord tissue from a presymptomatic transgenic rat model of amyotrophic lateral sclerosis. J. Neurosci. Res. 88, 2736-2746. <https://doi.org/10.1002/jnr.22424>
40. Shechter, R., Miller, O., Yovel, G., Rosenzweig, N., London, A., Ruckh, J., Kim, K. W., Klein, E., Kalchenko, V., Bendel, P., Lira, S. A., Jung, S., Schwartz, M. (2013) Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity 38, 555-569. <https://doi.org/10.1016/j.immuni.2013.02.012>
41. Sierra, A., Abiega, O., Shahraz, A., Neumann, H. (2013) Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis. Front. Cell. Neurosci. 7, 6. <https://doi.org/10.3389/fncel.2013.00006>
42. 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) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7, 483-495. <https://doi.org/10.1016/j.stem.2010.08.014>
43. Stuart, L. M., Bell, S. A., Stewart, C. R., Silver, J. M., Richard, J., Goss, J. L., Tseng, A. A., Zhang, A., El Khoury, J. B., Moore, K. J. (2007) CD36 signals to the actin cytoskeleton and regulates microglial migration via a p130Cas complex. J. Biol. Chem. 282, 27392-27401. <https://doi.org/10.1074/jbc.M702887200>
44. Takeuchi, H., Jin, S. J., Wang, J. Y., Zhang, G. Q., Kawanokuchi, J., Kuno, R., Sonobe, Y., Mizuno, T., Suzumura, A. (2006) Tumor necrosis factor-α induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J. Biol. Chem. 281, 21362-21368. <https://doi.org/10.1074/jbc.M600504200>
45. Thrash, J. C., Torbett, B. E., Carson, M. J. (2009) Developmental regulation of TREM2 and DAP12 expression in the murine CNS: implications for Nasu-Hakola disease. Neurochem. Res. 34, 38-45. <https://doi.org/10.1007/s11064-008-9657-1>
46. Van Ginderachter, J. A., Movahedi, K., Hassanzadeh Ghassabeh, G., Meerschaut, S., Beschin, A., Raes, G., De Baetselier, P. (2006) Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion. Immunobiology 211, 487-501. <https://doi.org/10.1016/j.imbio.2006.06.002>
47. Xie, Z., Harris-White, M. E., Wals, P. A., Frautschy, S. A., Finch, C. E., Morgan, T. E. (2005) Apolipoprotein J (clusterin) activates rodent microglia in vivo and in vitro. J. Neurochem. 93, 1038-1046. <https://doi.org/10.1111/j.1471-4159.2005.03065.x>
48. Zhang, F., Liu, J., Shi, J. S. (2010) Anti-inflammatory activities of resveratrol in the brain: role of resveratrol in microglial activation. Eur. J. Pharmacol. 636, 1-7. <https://doi.org/10.1016/j.ejphar.2010.03.043>
49. Zhu, S., Tai, C., Petkau, T. L., Zhang, S., Liao, C., Dong, Z., Wen, W., Chang, Q., Tian Wang, Y., MacVicar, B. A., Leavitt, B. R., Jia, W., Cynader, M. S. (2013) Progranulin promotes activation of microglia/macrophage after pilocarpine- induced status epilepticus. Brain Res. 1530, 54-65. <https://doi.org/10.1016/j.brainres.2013.07.023>
50. Zusso, M., Methot, L., Lo, R., Greenhalgh, A. D., David, S., Stifani, S. (2012) Regulation of postnatal forebrain amoeboid microglial cell proliferation and development by the transcription factor Runx1. J. Neurosci. 32, 11285-11298. <https://doi.org/10.1523/JNEUROSCI.6182-11.2012>
front cover

ISSN 0015-5500 (Print) ISSN 2533-7602 (Online)

Open access journal

Submissions

Archive