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Clinical Implications of Neuroscience Research
August 14, 2013
Letter to the Editor

Microglia
Multiple roles in surveillance, circuit shaping, and response to injury

September 17, 2013 issue
81 (12) 1079-1088

Abstract

Microglial cells are the immune cells in the CNS and represent approximately 10% of the total brain cell population. Their morphologic characterization by Pio del Rio-Hortega was first published almost a century ago, but the understanding of their function in the normal and injured CNS is still incomplete. Classically, microglia have been classified into 2 main types: “resting” microglia, with a ramified morphology, present in the uninjured CNS; and “activated” microglia, with an amoeboid morphology, present at the sites of injury. However, morphologic, molecular, and genetic studies indicate that this subdivision is a misleading oversimplification. Resting microglia actively survey their environment; activated microglia constitute a heterogeneous population that dynamically changes in phenotype depending on the type of stimulus and microenvironment, participating not only in mechanisms of injury but also in neuroprotection, repair, and circuit refinement in the CNS. The primary role of microglia is therefore to maintain cellular, synaptic, and myelin homeostasis both during development and normal function of the CNS and in response to CNS injury. Microglia have been implicated in mechanisms of CNS trauma, stroke, infection, demyelination, neoplasm, and neurodegeneration. Microglial dysfunction may also contribute to genetic neurobehavioral disorders, such as Rett syndrome. There are several comprehensive reviews on all these topics.1–12

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Letters to the Editor
24 November 2013
Microglia: Multiple roles in surveillance, circuit shaping, and response to injury
Christina Sundal, : Department of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg
: Department of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
Dr. Benarroch provided an excellent overview of the role of microglia. [1] Microglia are implicated in many neurodegenerative disorders and we note that the newly identified colony stimulating factor 1 receptor (CSF1R) gene mutation is causative for the brain white matter disorder hereditary diffuse leukoencephalopathy with spheroids (HDLS). [2] HDLS is an inherited, progressive disorder of axons and myelin with a variable phenotype, mimicking other disorders such as primary progressive multiple sclerosis, frontotemporal and other dementias, or atypical parkinsonian disorders. [2, 3] The CSF1R gene encodes a tyrosine kinase transmembrane receptor for the cytokine CSF1, which is trophic for phagocytic cells of the myeloid lineage--including microglia-- and for interleukin 34 (IL-34). [4] It is well known that lipid-laden microglia are a consistent microscopic finding in HDLS pathology. The CSF1R gene mutation thus establishes HDLS as a microgliopathy. [2] However, the exact mechanism is still unclear. It may be related to an abnormal innate immune response predisposing to neurodegeneration. Discovering the role of CSF1R signaling in HDLS might offer novel insights into microglial physiology and the involvement of this cell type in neurodegeneration.

1. Benarroch EE. Microglia: Multiple roles in surveillance, circuit shaping, and response to injury. Neurology 2013;81:1079-1088. 2. Rademakers R, Baker M, Nicholson AM, et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat Genet 2012;44:200-205. 3. Sundal C, Lash J, Aasly J, et al. Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): a misdiagnosed disease entity. J Neurol Sci 2012;314:130-137. 4. Zelante T, Ricciardi-Castagnoli P. The yin-yang nature of CSF1R-binding cytokines. Nature immunology 2012;13:717-719.

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Neurology®
Volume 81Number 12September 17, 2013
Pages: 1079-1088
PubMed: 23946308

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Published online: August 14, 2013
Published in print: September 17, 2013

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Eduardo E. Benarroch, MD
From the Department of Neurology, Mayo Clinic, Rochester, MN.
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Notes

Correspondence to Dr. Benarroch: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the author, if any, are provided at the end of the article.

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