Role of Microglia in Multiple Sclerosis

Glial cells play many critical roles in the mediation of immune responses, transmission of axon potentials and maintenance of CNS (central nervous system) homeostasis. Demyelination refers to the loss of the myelin sheath, which affects the ability of the neurons to signal appropriately.

Demyelination can occur in the peripheral and central nervous system in response to viral infection, inflammatory disease or toxic insult. Table 1 shows several demyelinating diseases, of which multiple sclerosis or MS is perhaps the most well-known medical condition.

Despite the detailed description of the pathological and clinical features of multiple sclerosis, its etiology continues to be a mystery.

Table 1. Demyelinating diseases.


Multiple sclerosis


Acute-hemorrhagic leucoencephalitis


Combined central and peripheral demyelination

Guillan-Barré Syndrome

Peripheral nerve demyelination


Neuromyelitis Optica

PML (Viral demyelination)

Progressive multifocal leukoencephalopathy

SSPE (Viral demyelination)

Subacute scerosing panencephalitis


The series of events leading to demyelination in the nervous system is vastly complex and is characterized by interactions between infiltrating and resident immune cells (usually auto-immune, Table 2), the glial cells containing nervous tissue and neurons.

Table 2. Autoantibodies in demyelination.






Experimental Autoimmune Encephalomyelitis (EAE)

Myelin components (gangliosides, glycoproteins etc.)




Aquaporin 4



When demyelination occurs, the myelin generated by oligodendrocytes is lost from around axons and apoptotic cell death of the oligodendrocyte may occur. This is accompanied by an influx of macrophages, T cells and B cells from the periphery along with the activation and proliferation of microglial cells residing in the CNS.

There is some evidence that, in demyelinating diseases, this inflammation is exacerbated by defects in, or damage to the blood-brain barrier (BBB). This highly impermeable barrier between CNS and blood is formed by endothelial cells. Research has demonstrated a reduced expression of the occludin and claudin-5 proteins at the BBB, while the ZO-1 is simultaneously relocated in this structure.

When microglial cells are activated, they become polarized into distinct phenotypes, of which M1 and M2 are the best described. M1 microglia, characterized by expression of pro-inflammatory molecules such as TNFα, iNOS, HLA-DR and TLRs and are found to occur early in demyelination.

They are very important in terms of antigen presentation, infiltrating macrophages from the periphery, phagocytosis of apoptotic cells and myelin debris, and in the generation of chemokine and cytokine profiles that help sustain a pro-inflammatory environment.

By contrast, M2 microglia are characterized by expression of TGFβ and Arg-1 molecules. They help promote regeneration and are likely to dominate at a later phase of the demyelination process. M2 microglia are involved in the recruitment of oligodendrocyte progenitors; matured oligodendrocyte progenitors remyelinate the denuded axons. Undoubtedly, the ratio of M2:M1 microglia is believed to be important in allowing an environment that is permissive for successful remyelination.

Another important player in the pathogenesis of demyelination is astrocytes. Since myelin is lost from the axon, glial fibrillary acidic protein (GFAP) is proliferated and upregulated by astrocytes through a process called "astrogliosis" – a hallmark of various CNS diseases.

Astrocytes have protective effects on neurons and also play a role in the maintenance of the BBB. These cells also perform many other different functions in the CNS, especially in inflammatory demyelination.

Astrocytes are similar to microglia and also express a wide range of inflammation-related molecules. They can execute antigen presentation and generate chemokine and cytokine profiles, which have intense effects on resident microglia and also on the infiltrating macrophages, B cells and T cells.

Just like microglia, these responses can either be inhibitory and pro-inflammatory for demyelination, or neuroprotective in that they can reduce the inflammation mediated by the T-cells and promote upregulation of neuroprotective molecules.

Suggested Reading

  1. Barnett SC, Linnington C, 2013. Myelination: do astrocytes play a role? Neurosci, 19, 442-450.
  2. Barres BA, 2008. The mystery and magic of glia: a perspective on their roles in health and disease.Neuron, 60, 430-440.
  3. Blackburn D, Sargsyan S, Monk PN, Shaw PJ, 2009. Astrocyte function and role in motor neuron disease: a future therapeutic target? Glia, 57, 1251-1264.
  4. Bomprezzi R, Campagnolo D, 2009. Inflammatory Demyelinating Diesease of the Central.Barrow Q. 24.
  5. Brosnan CF, Raine CS, 2013. The astrocyte in multiple sclerosis revisited.Glia, 61, 453-465.
  6. Carpentier PA, Duncan DS, Miller DS, 2008. Abcam poster TLR br inf autoimm Carpentier 2008 Br Behav Imm.pdf. Brain Behav Immun, 22, 140-147.
  7. Claycomb KI, Johnson KM, Winokur PN, Sacino AV, Crocker SJ, 2013. Astrocyte regulation of CNS inflammation and remyelination.Brain Sci, 3, 1109-1127.
  8. Goldenburg MM, 2012. Multiple sclerosis review.PT, 37, 175-184.
  9. Gudi V, Gingele S, Skripuletz T, Stangel M, 2014. Glial response during cuprizone-induced de- and remyelination in the CNS: Lessons learned.Front Cell Neurosci, 8, 73.
  10. Kipp M, van der Star BJ, Vogel DYS, Puentes F, van der Valk P, Baker D, Amor S, 2012. Experimental in vivo and in vitro models of multiple sclerosis: EAE and beyond.Mult Scler Relat Disord, 1, 15-28.
  11. Love S, 2006. Demyelinating diseases.J Clin Pathol, 59, 1151-1159.
  12. Lucchinetti C, Brück W, Paris J, Scheithauer B, Rodriguez M, Lassmann H, 2000. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol, 47, 707-717.
  13. Montgomery DL, 1994. Astrocytes: Form, Functions, and Roles in Disease. Vet Pathol, 31, 145-167.
  14. Nair A, Frederick, TJ, Miller SD, 2008. Astrocytes in multiple sclerosis: a product of their environment. Cell Mol Life Sci, 65, 2702-2720.
  15. Napoli I, Neumann H, 2010. Protective effects of microglia in multiple sclerosis. Exp Neurol, 225, 24-28.
  16. Popescu BFG, Lucchinetti CF, 2012. Pathology of demyelinating diseases. Annu Rev Pathol, 7, 185-217.
  17. Ridet JL, Malhotra SK, Privat A, Gage FH, 1997. Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci, 20, 570-577.
  18. Saijo K, Glass CK, 2011. Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol, 11, 775-787.
  19. Saikali P, Cayrol R, Vincent T, 2009. Anti-aquaporin-4 auto-antibodies orchestrate the pathogenesis in neuromyelitis optica. Autoimmun Rev, 9, 132-135.
  20. Sharma R, Fischer MT, Bauer J, Felts PA, Smith KJ, Misu T, Fujihara K, Bradl M, Lassmann H, 2010. Inflammation induced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demyelination. Acta Neuropathol, 120, 223-326.
  21. Sheikh AM, Nagai A, Ryu JK, McLarnon JG, Kim SU, Masuda J, 2009. Lysophosphatidylcholine induces glial cells activation: role of rho kinase. Glia, 57, 898-907.
  22. Skripuletz T, Hackstette D, Bauer K, Gudi V, Pul R, Voss E, Berger K, Kipp M, Baumgärter W, Stangel M, 2013. Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain, 136, 147-167.
  23. Vincent T, Saikali P, Cayrol R, Roth AD, Bar-Or A, Prat A, Antel JP, 2008. Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood-brain barrier permeability and granulocyte recruitment.

About Abcam

Abcam is a global life sciences company providing highly validated antibodies and other binders and assays to the research and clinical communities to help advance the understanding of biology and causes of disease.

Abcam’s mission is to serve life scientists to help them achieve their mission faster by listening to their needs, continuously innovating and improving and by giving them the tools, data and experience they want. Abcam’s ambition is to become the most influential life science company for researchers worldwide.

Sponsored Content Policy: publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of News-Medical.Net which is to educate and inform site visitors interested in medical research, science, medical devices and treatments.

Last updated: Jun 3, 2019 at 9:43 AM


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Abcam. (2019, June 03). Role of Microglia in Multiple Sclerosis. News-Medical. Retrieved on November 18, 2019 from

  • MLA

    Abcam. "Role of Microglia in Multiple Sclerosis". News-Medical. 18 November 2019. <>.

  • Chicago

    Abcam. "Role of Microglia in Multiple Sclerosis". News-Medical. (accessed November 18, 2019).

  • Harvard

    Abcam. 2019. Role of Microglia in Multiple Sclerosis. News-Medical, viewed 18 November 2019,

Other White Papers by this Supplier