Chapter 12 : Microglia

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Microglia, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap12-1.gif /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap12-2.gif


Microglia are the resident macrophages of the brain parenchyma ( ). Although it has long been known that microglia are of myeloid lineage, based on immunocytochemical detection of macrophage-restricted antigens ( ), it has only relatively recently been shown, by fate mapping studies, that these cells are of yolk sac origin and enter the developing neuroepithelium of the central nervous system (CNS) in the embryo ( ). They are present throughout the length of the neuraxis, characterized by their fine processes emanating from a small cell body, and each cell appears to occupy its own territory. The morphology of microglia and their territorial behavior is well illustrated in retina whole mounts ( Fig. 1 ). The density and morphology of the microglia vary between distinct functional divisions of the CNS, with the lowest density found in the cerebellum and perhaps the highest density in the substantia nigra ( ). These regional differences have been well studied in rodents, the most common experimental animal models, and although similar regional differences are seen in the human brain, there are some notable differences. In the rodent brain, the microglia are denser in gray matter than in white matter, while in the human brain, the microglia are denser in the large-fiber tracts that dominate the larger brain ( ).

Citation: Perry V. 2017. Microglia, p 225-233. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0003-2015
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Microglia in the outer plexiform layer of the retina of the mouse, illustrating the delicate branching of the processes and the territory occupied by each cell. GFP-labeled cell from a MacGreen mouse with immunocytochemistry. Courtesy of Sallome Murinello.

Citation: Perry V. 2017. Microglia, p 225-233. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0003-2015
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Electron micrograph of a microglia in the adult mouse cortex immunolabeled with F4/80. The thin rim of cytoplasm and the sparse rough endoplasmic reticulum point to the downregulated phenotype of these cells. Ligands expressed in the CNS (left-hand column) engage receptors expressed on the microglia (right-hand column) that inhibit their activation. Other soluble mediators, including the neurotransmitters acetylcholine (ACh) and noradrenaline (NA), are shown at the top of the figure.

Citation: Perry V. 2017. Microglia, p 225-233. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0003-2015
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

GFP-labeled microglia in the hippocampus of the normal adult mouse , and morphologically activated microglia in the hippocampus of a mouse with prion disease . Note the greater density of cells, larger cell bodies, and multiple processes of those in panel B compared to panel A. Courtesy of Diego Gomez-Nicola.

Citation: Perry V. 2017. Microglia, p 225-233. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0003-2015
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ransohoff RM,, Perry VH . 2009. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 27 : 119 145.[PubMed] [CrossRef]
2. Perry VH,, Hume DA,, Gordon S . 1985. Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15 : 313 326.[PubMed] [CrossRef]
3. Ginhoux F,, Greter M,, Leboeuf M,, Nandi S,, See P,, Gokhan S,, Mehler MF,, Conway SJ,, Ng LG,, Stanley ER,, Samokhvalov IM,, Merad M . 2010. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330 : 841 845.[PubMed] [CrossRef]
4. Lawson LJ,, Perry VH,, Gordon S . 1992. Turnover of resident microglia in the normal adult mouse brain. Neuroscience 48 : 405 415.[PubMed] [CrossRef]
5. Mittelbronn M,, Dietz K,, Schluesener HJ,, Meyermann R . 2001. Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude. Acta Neuropathol 101 : 249 255.[PubMed]
6. Nimmerjahn A,, Kirchhoff F,, Helmchen F . 2005. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308 : 1314 1318.[PubMed] [CrossRef]
7. Hefendehl JK,, Neher JJ,, Sühs RB,, Kohsaka S,, Skodras A,, Jucker M . 2014. Homeostatic and injury-induced microglia behavior in the aging brain. Aging Cell 13 : 60 69.[PubMed] [CrossRef]
8. Hickman SE,, Kingery ND,, Ohsumi TK,, Borowsky ML,, Wang LC,, Means TK,, El Khoury J . 2013. The microglial sensome revealed by direct RNA sequencing. Nat Neurosci 16 : 1896 1905.[PubMed] [CrossRef]
9. Butovsky O,, Jedrychowski MP,, Moore CS,, Cialic R,, Lanser AJ,, Gabriely G,, Koeglsperger T,, Dake B,, Wu PM,, Doykan CE,, Fanek Z,, Liu L,, Chen Z,, Rothstein JD,, Ransohoff RM,, Gygi SP,, Antel JP,, Weiner HL . 2014. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 17 : 131 143.[PubMed] [CrossRef]
10. Kettenmann H,, Hanisch UK,, Noda M,, Verkhratsky A . 2011. Physiology of microglia. Physiol Rev 91 : 461 553.[PubMed] [CrossRef]
11. Lawson LJ,, Perry VH,, Gordon S . 1992. Turnover of resident microglia in the normal adult mouse brain. Neuroscience 48 : 405 415.[PubMed] [CrossRef]
12. Mildner A,, Schlevogt B,, Kierdorf K,, Böttcher C,, Erny D,, Kummer MP,, Quinn M,, Brück W,, Bechmann I,, Heneka MT,, Priller J,, Prinz M . 2011. Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer’s disease. J Neurosci 31 : 11159 11171.[PubMed] [CrossRef]
13. Tremblay ,, Lowery RL,, Majewska AK . 2010. Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8 : e1000527. doi:10.1371/journal.pbio.1000527. [PubMed] [CrossRef]
14. Sogn CJ,, Puchades M,, Gundersen V . 2013. Rare contacts between synapses and microglial processes containing high levels of Iba1 and actin—a postembedding immunogold study in the healthy rat brain. Eur J Neurosci 38 : 2030 2040.[PubMed] [CrossRef]
15. Satoh J,, Tabunoki H,, Ishida T,, Yagishita S,, Jinnai K,, Futamura N,, Kobayashi M,, Toyoshima I,, Yoshioka T,, Enomoto K,, Arai N,, Arima K . 2011. Immunohistochemical characterization of microglia in Nasu-Hakola disease brains. Neuropathology 31 : 363 375.[PubMed] [CrossRef]
16. Nicholson AM,, Baker MC,, Finch NA,, Rutherford NJ,, Wider C,, Graff-Radford NR,, Nelson PT,, Clark HB,, Wszolek ZK,, Dickson DW,, Knopman DS,, Rademakers R . 2013. CSF1R mutations link POLD and HDLS as a single disease entity. Neurology 80 : 1033 1040.[PubMed] [CrossRef]
17. Krämer-Albers EM,, Bretz N,, Tenzer S,, Winterstein C,, Möbius W,, Berger H,, Nave KA,, Schild H,, Trotter J . 2007. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: trophic support for axons? Proteomics Clin Appl 1 : 1446 1461.[PubMed] [CrossRef]
18. Streit WJ,, Xue QS . 2014. Human CNS immune senescence and neurodegeneration. Curr Opin Immunol 29 : 93 96.[PubMed] [CrossRef]
19. Dantzer R,, O’Connor JC,, Freund GG,, Johnson RW,, Kelley KW . 2008. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9 : 46 56.[PubMed] [CrossRef]
20. Tracey KJ . 2007. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 117 : 289 296.[PubMed] [CrossRef]
21. Lacroix S,, Feinstein D,, Rivest S . 1998. The bacterial endotoxin lipopolysaccharide has the ability to target the brain in upregulating its membrane CD14 receptor within specific cellular populations. Brain Pathol 8 : 625 640.[PubMed] [CrossRef]
22. Teeling JL,, Perry VH . 2009. Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: underlying mechanisms. Neuroscience 158 : 1062 1073.[PubMed] [CrossRef]
23. Hannestad J,, Gallezot JD,, Schafbauer T,, Lim K,, Kloczynski T,, Morris ED,, Carson RE,, Ding YS,, Cosgrove KP . 2012. Endotoxin-induced systemic inflammation activates microglia: [ 11C]PBR28 positron emission tomography in nonhuman primates. Neuroimage 63 : 232 239.[PubMed] [CrossRef]
24. Stevens B,, Allen NJ,, Vazquez LE,, Howell GR,, Christopherson KS,, Nouri N,, Micheva KD,, Mehalow AK,, Huberman AD,, Stafford B,, Sher A,, Litke AM,, Lambris JD,, Smith SJ,, John SW,, Barres BA . 2007. The classical complement cascade mediates CNS synapse elimination. Cell 131 : 1164 1178.[PubMed] [CrossRef]
25. Paolicelli RC,, Bolasco G,, Pagani F,, Maggi L,, Scianni M,, Panzanelli P,, Giustetto M,, Ferreira TA,, Guiducci E,, Dumas L,, Ragozzino D,, Gross CT . 2011. Synaptic pruning by microglia is necessary for normal brain development. Science 333 : 1456 1458.[PubMed] [CrossRef]
26. Kreutzberg GW . 1996. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19 : 312 318.[PubMed] [CrossRef]
27. Sawcer S,, Franklin RJ,, Ban M . 2014. Multiple sclerosis genetics. Lancet Neurol 13 : 700 709.[PubMed] [CrossRef]
28. Hickey WF,, Kimura H . 1988. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239 : 290 292.[PubMed] [CrossRef]
29. Huitinga I,, van Rooijen N,, de Groot CJ,, Uitdehaag BM,, Dijkstra CD . 1990. Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J Exp Med 172 : 1025 1033.[PubMed] [CrossRef]
30. Ajami B,, Bennett JL,, Krieger C,, McNagny KM,, Rossi FM . 2011. Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci 14 : 1142 1149.[PubMed] [CrossRef]
31. Yamasaki R,, Lu H,, Butovsky O,, Ohno N,, Rietsch AM,, Cialic R,, Wu PM,, Doykan CE,, Lin J,, Cotleur AC,, Kidd G,, Zorlu MM,, Sun N,, Hu W,, Liu L,, Lee JC,, Taylor SE,, Uehlein L,, Dixon D,, Gu J,, Floruta CM,, Zhu M,, Charo IF,, Weiner HL,, Ransohoff RM . 2014. Differential roles of microglia and monocytes in the inflamed central nervous system. J Exp Med 211 : 1533 1549.[PubMed] [CrossRef]
32. Heneka MT,, Carson MJ,, El Khoury J,, Landreth GE,, Brosseron F,, Feinstein DL,, Jacobs AH,, Wyss-Coray T,, Vitorica J,, Ransohoff RM,, Herrup K,, Frautschy SA,, Finsen B,, Brown GC,, Verkhratsky A,, Yamanaka K,, Koistinaho J,, Latz E,, Halle A,, Petzold GC,, Town T,, Morgan D,, Shinohara ML,, Perry VH,, Holmes C,, Bazan NG,, Brooks DJ,, Hunot S,, Joseph B,, Deigendesch N,, Garaschuk O,, Boddeke E,, Dinarello CA,, Breitner JC,, Cole GM,, Golenbock DT,, Kummer MP . 2015. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 14 : 388 405.[PubMed] [CrossRef]
33. Karch CM,, Goate AM . 2015. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry 77 : 43 51.[PubMed] [CrossRef]
34. Webster SJ,, Bachstetter AD,, Nelson PT,, Schmitt FA,, Van Eldik LJ . 2014. Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet 5 : 88. doi:10.3389/fgene.2014.00088. [PubMed] [CrossRef]
35. Grathwohl SA,, Kälin RE,, Bolmont T,, Prokop S,, Winkelmann G,, Kaeser SA,, Odenthal J,, Radde R,, Eldh T,, Gandy S,, Aguzzi A,, Staufenbiel M,, Mathews PM,, Wolburg H,, Heppner FL,, Jucker M . 2009. Formation and maintenance of Alzheimer’s disease β-amyloid plaques in the absence of microglia. Nat Neurosci 12 : 1361 1363.[PubMed] [CrossRef]
36. Simard AR,, Soulet D,, Gowing G,, Julien JP,, Rivest S . 2006. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49 : 489 502.[PubMed] [CrossRef]
37. Guillot-Sestier MV,, Doty KR,, Gate D,, Rodriguez J Jr,, Leung BP,, Rezai-Zadeh K,, Town T . 2015. Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology. Neuron 85 : 534 548.[PubMed] [CrossRef]
38. Schenk D,, Barbour R,, Dunn W,, Gordon G,, Grajeda H,, Guido T,, Hu K,, Huang J,, Johnson-Wood K,, Khan K,, Kholodenko D,, Lee M,, Liao Z,, Lieberburg I,, Motter R,, Mutter L,, Soriano F,, Shopp G,, Vasquez N,, Vandevert C,, Walker S,, Wogulis M,, Yednock T,, Games D,, Seubert P . 1999. Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400 : 173 177.[PubMed] [CrossRef]
39. Karran E,, Hardy J . 2014. A critique of the drug discovery and phase 3 clinical programs targeting the amyloid hypothesis for Alzheimer disease. Ann Neurol 76 : 185 205.[PubMed] [CrossRef]
40. Gómez-Nicola D,, Fransen NL,, Suzzi S,, Perry VH . 2013. Regulation of microglial proliferation during chronic neurodegeneration. J Neurosci 33 : 2481 2493.[PubMed] [CrossRef]
41. Deckers K,, van Boxtel MP,, Schiepers OJ,, de Vugt M,, Muñoz Sánchez JL,, Anstey KJ,, Brayne C,, Dartigues JF,, Engedal K,, Kivipelto M,, Ritchie K,, Starr JM,, Yaffe K,, Irving K,, Verhey FR,, Köhler S . 2015. Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies. Int J Geriatr Psychiatry 30 : 234 246.[PubMed] [CrossRef]
42. Cunningham C,, Campion S,, Lunnon K,, Murray CL,, Woods JF,, Deacon RM,, Rawlins JN,, Perry VH . 2009. Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry 65 : 304 312.[PubMed] [CrossRef]
43. Perry VH,, Holmes C . 2014. Microglial priming in neurodegenerative disease. Nat Rev Neurol 10 : 217 224.[PubMed] [CrossRef]
44. Paniagua RT,, Chang A,, Mariano MM,, Stein EA,, Wang Q,, Lindstrom TM,, Sharpe O,, Roscow C,, Ho PP,, Lee DM,, Robinson WH . 2010. c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis. Arthritis Res Ther 12 : R32. doi:10.1186/ar2940. [PubMed] [CrossRef]
45. Maclullich AM,, Anand A,, Davis DH,, Jackson T,, Barugh AJ,, Hall RJ,, Ferguson KJ,, Meagher DJ,, Cunningham C . 2013. New horizons in the pathogenesis, assessment and management of delirium. Age Ageing 42 : 667 674.[PubMed] [CrossRef]
46. Holmes C,, Cunningham C,, Zotova E,, Woolford J,, Dean C,, Kerr S,, Culliford D,, Perry VH . 2009. Systemic inflammation and disease progression in Alzheimer disease. Neurology 73 : 768 774.[PubMed] [CrossRef]

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error