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The microglia cells function in the CNS like specialized macrophages and are derived from haematopoietic type precursors that have migrated from the periphery, mainly before birth. A microglial phenotype, evolves which clearly distinguish them from monocytes. They have key roles in a large number of neurological and psychological conditions ranging from encephalitis to schizophrenia[1][2]



Under usual conditions the microglia are the most physically active cells in the brain. Resting microglial cells have a small cell body with thin processes that actively extend and contract at rates approaching 3 µm/min in all directions patrolling a territory, about 15 - 30 µm wide. The processes can rest for periods of minutes at sites of synaptic contacts and activity is sensitive to activators such as ATP and inhibitors of purinergic receptors.


Neuronal damage induces the movement of microglial processes towards the lesion. This is a process that depends upon activation of purinergic receptors, and which is modulated by inhibition of astrocyte gap junctions , with the astrocytes signaling to the microglia by releasing messengers such as ATP through connexin hemichannels[3]. There follows a gradual transformation of the microglia cell into an ameboid form through several stages:

  1. Resting microglia retract their processes, which become fewer and thicker, with an increase in cell body size. Immune response molecules start to produced and some microglial cells change to a proliferative mode.
  2. Microglial proliferation occurs as well as microglia cells moving by amoeboid-like activity to the site of insult.
  3. With neuronal death some microglia transform into phagocytes.

Microglia have two alternative activation phenotypes[4]:

  1. M1 (pro-inflammatory) phenotype
  2. M2 (anti-inflammatory) phenotype


Microglia express many of the classical neurotransmitter receptors ( eg receptors for GABA, glutamate, dopamine, and noradrenaline. In most cases, activation of such receptors counteracts the activation of microglia and prevents them developing activated phenotypes. They also express receptors that detect molecules released by damaged neurons such as ATP, cytokines, neuropeptides, nitric oxide or ammonia. Some such molecules initiate microglial migration and act as chemoattractants, including ATP, cannabinoids, lysophosphatidic acid and bradykinin. The various ion channels and transporters expressed on the microglia cell surface change during this process.CX3CL1-CX3CR1 signalling negatively regulates microglial activation and protects dopaminergic neurons from degeneration induced by neurotoxins[5]. Dysfunction of CD200-CD200R signalling also activates microglia and is associated with the degeneration of dopaminergic neurons[6].


The apoptotic process is central to CNS development and is not just pathological. However it can become pathological and the beta-amyloid of Alzheimers disease, changes seen at post motem in Parkinsons disease[4] and myelin fragments of multiple sclerosis result from microglia activity. Indeed all these conditions and others such as schizophrenia are associated with positron emission tomography (PET) evidence of pronounced activation of microglia.

Antigen presentation

Microglia are the dominant antigen presenting cells in the CNS. On their activation the major histocompatibility complex II (MHCII) and co-stimulatory molecules such as CD80, CD86 and CD40 are expressed. These can produce interaction with T cells migrating into the CNS and recruitment of leucocytes.


  1. Laskaris LE, Di Biase MA, Everall I, Chana G, Christopoulos A, Skafidas E, Cropley VL, Pantelis C. Microglial activation and progressive brain changes in schizophrenia. British journal of pharmacology. 2015 Oct 12.(Epub ahead of print) (Link to article – subscription may be required.)
  2. Bloomfield PS, Selvaraj S, Veronese M, Rizzo G, Bertoldo A, Owen DR, Bloomfield MA, Bonoldi I, Kalk N, Turkheimer F, McGuire P, de Paola V, Howes OD. Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An (11)C.PBR28 PET Brain Imaging Study. The American journal of psychiatry. 2015 Oct 16; :appiajp201514101358.(Epub ahead of print) (Link to article – subscription may be required.)
  3. Koizumi S, Ohsawa K, Inoue K, Kohsaka S. Purinergic receptors in microglia: functional modal shifts of microglia mediated by P2 and P1 receptors. Glia. 2013 Jan; 61(1):47-54.(Link to article – subscription may be required.)
  4. a b Wang Q, Liu Y, Zhou J. Neuroinflammation in Parkinson's disease and its potential as therapeutic target. Translational neurodegeneration. 2015; 4:19.(Epub) (Link to article – subscription may be required.)
  5. Pabon MM, Bachstetter AD, Hudson CE, Gemma C, Bickford PC. CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson's disease. Journal of neuroinflammation. 2011; 8:9.(Epub) (Link to article – subscription may be required.)
  6. Wang XJ, Zhang S, Yan ZQ, Zhao YX, Zhou HY, Wang Y, Lu GQ, Zhang JD. Impaired CD200-CD200R-mediated microglia silencing enhances midbrain dopaminergic neurodegeneration: roles of aging, superoxide, NADPH oxidase, and p38 MAPK. Free radical biology & medicine. 2011 May 1; 50(9):1094-106.(Link to article – subscription may be required.)

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