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PMID: 18567623 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Debris clearance by microglia: an essential link between degeneration and regeneration.

Brain : a journal of neurology ·Vol. 132 ·No. Pt 2 ·2009-02-00 ·Pages 288-95

Neumann H, Kotter MR, Franklin RJ

Abstract

Microglia are cells of myeloid origin that populate the CNS during early development and form the brain's innate immune cell type. They perform homoeostatic activity in the normal CNS, a function associated with high motility of their ramified processes and their constant phagocytic clearance of cell debris. This debris clearance role is amplified in CNS injury, where there is frank loss of tissue and recruitment of microglia to the injured area. Recent evidence suggests that this phagocytic clearance following injury is more than simply tidying up, but instead plays a fundamental role in facilitating the reorganization of neuronal circuits and triggering repair. Insufficient clearance by microglia, prevalent in several neurodegenerative diseases and declining with ageing, is associated with an inadequate regenerative response. Thus, understanding the mechanism and functional significance of microglial-mediated clearance of tissue debris following injury may open up exciting new therapeutic avenues.

MeSH Terms
Aging/immunology Brain/immunology,pathology Cytokines/immunology Humans Microglia/physiology Nerve Regeneration/physiology Neurodegenerative Diseases/immunology,pathology Phagocytosis/physiology
Chemicals
Cytokines
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Neumann H
Neural Regeneration, Institute of Reconstructive Neurobiology, University Bonn and Hertie-Foundation, Bonn, Germany. hneuman1@uni-bonn.de
Kotter M R
Franklin R J M
References (71)
71 references, click to expand
  1. Microglial senescence: does the brain's immune system have an expiration date?
    Trends Neurosci. 2006 Sep;29(9):506-10 PMID: 16859761
  2. Remyelination can be extensive in multiple sclerosis despite a long disease course.
    Neuropathol Appl Neurobiol. 2007 Jun;33(3):277-87 PMID: 17442065
  3. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain.
    Nature. 2005 Dec 15;438(7070):1017-21 PMID: 16355225
  4. Filopodia act as phagocytic tentacles and pull with discrete steps and a load-dependent velocity.
    Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11633-8 PMID: 17620618
  5. IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes.
    J Cell Biol. 2004 Jan 5;164(1):111-22 PMID: 14709544
  6. Axon pruning: an active role for glial cells.
    Curr Biol. 2004 Apr 20;14(8):R302-4 PMID: 15084298
  7. Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation.
    J Neurosci. 2006 Jan 4;26(1):328-32 PMID: 16399703
  8. TNF-alpha suppresses CR3-mediated myelin removal by macrophages.
    J Neuroimmunol. 1992 May;38(1-2):9-17 PMID: 1349613
  9. CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion.
    J Neurosci. 2004 Sep 29;24(39):8500-9 PMID: 15456824
  10. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2.
    J Exp Med. 2005 Feb 21;201(4):647-57 PMID: 15728241
  11. Axon branch removal at developing synapses by axosome shedding.
    Neuron. 2004 Nov 18;44(4):651-61 PMID: 15541313
  12. Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions.
    Nat Neurosci. 2007 Dec;10(12):1544-53 PMID: 18026096
  13. Microglia-derived nerve growth factor causes cell death in the developing retina.
    Neuron. 1998 Jan;20(1):35-41 PMID: 9459440
  14. Microglia: active sensor and versatile effector cells in the normal and pathologic brain.
    Nat Neurosci. 2007 Nov;10(11):1387-94 PMID: 17965659
  15. The role of microglia and macrophages in the pathophysiology of the CNS.
    Prog Neurobiol. 1999 Jun;58(3):233-47 PMID: 10341362
  16. Phenotypic diversity and kinetics of proliferating microglia and astrocytes following cortical stab wounds.
    Glia. 1996 Apr;16(4):368-82 PMID: 8721677
  17. Synaptic scaling mediated by glial TNF-alpha.
    Nature. 2006 Apr 20;440(7087):1054-9 PMID: 16547515
  18. The microglial networks of the brain and their role in neuronal network plasticity after lesion.
    Brain Res Rev. 2007 Aug;55(1):89-96 PMID: 17509690
  19. Receptor-mediated phagocytosis of myelin by macrophages and microglia: effect of opsonization and receptor blocking agents.
    Neurochem Res. 1996 Apr;21(4):481-7 PMID: 8734442
  20. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease.
    Nature. 2008 Feb 7;451(7179):720-4 PMID: 18256671
  21. Molecular approaches to spinal cord repair.
    Annu Rev Neurosci. 2003;26:411-40 PMID: 12626698
  22. The long-distance effects of brain lesions: visualization of myelinated pathways in the human brain using polarizing and fluorescence microscopy.
    J Neuropathol Exp Neurol. 1991 Jan;50(1):1-15 PMID: 1702142
  23. Remyelination is extensive in a subset of multiple sclerosis patients.
    Brain. 2006 Dec;129(Pt 12):3165-72 PMID: 16921173
  24. Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cuprizone toxicity.
    Lab Invest. 1978 Dec;39(6):597-612 PMID: 739762
  25. Remyelination occurs as extensively but more slowly in old rats compared to young rats following gliotoxin-induced CNS demyelination.
    Glia. 1999 Oct;28(1):77-83 PMID: 10498825
  26. Establishing a nursing center: learning from the literature and the experiences of others.
    J Prof Nurs. 1995 Jul-Aug;11(4):203-12 PMID: 7665795
  27. Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination.
    Neurobiol Aging. 2006 Sep;27(9):1298-307 PMID: 16051398
  28. Bone-marrow-derived cells contribute to the recruitment of microglial cells in response to beta-amyloid deposition in APP/PS1 double transgenic Alzheimer mice.
    Neurobiol Dis. 2005 Feb;18(1):134-42 PMID: 15649704
  29. Chronic demyelination inhibits remyelination in the central nervous system. An analysis of contributing factors.
    Lab Invest. 1980 Oct;43(4):382-7 PMID: 7442125
  30. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms.
    Nat Rev Neurosci. 2007 Jan;8(1):57-69 PMID: 17180163
  31. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis.
    PLoS Med. 2007 Apr;4(4):e124 PMID: 17425404
  32. Microglia and neuroprotection: implications for Alzheimer's disease.
    Brain Res Brain Res Rev. 2005 Apr;48(2):234-9 PMID: 15850662
  33. Control of microglial neurotoxicity by the fractalkine receptor.
    Nat Neurosci. 2006 Jul;9(7):917-24 PMID: 16732273
  34. Microglia promote the death of developing Purkinje cells.
    Neuron. 2004 Feb 19;41(4):535-47 PMID: 14980203
  35. Microglia derived from aging mice exhibit an altered inflammatory profile.
    Glia. 2007 Mar;55(4):412-24 PMID: 17203473
  36. Insulin-like growth factor I, but not neurotrophin-3, sustains Akt activation and provides long-term protection of immature oligodendrocytes from glutamate-mediated apoptosis.
    Mol Cell Neurosci. 2002 Jul;20(3):476-88 PMID: 12139923
  37. Macrophages and Microglia Produce Local Trophic Gradients That Stimulate Axonal Sprouting Toward but Not beyond the Wound Edge.
    Mol Cell Neurosci. 2002 Nov;21(3):436-53 PMID: 12498785
  38. Macrophages, microglia, and astrocytes are rapidly activated after crush injury of the goldfish optic nerve: a light and electron microscopic analysis.
    J Comp Neurol. 1995 Apr 3;354(2):306-20 PMID: 7540185
  39. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury.
    Exp Neurol. 1999 Aug;158(2):351-65 PMID: 10415142
  40. The classical complement cascade mediates CNS synapse elimination.
    Cell. 2007 Dec 14;131(6):1164-78 PMID: 18083105
  41. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life.
    Nat Neurosci. 2007 Dec;10(12):1538-43 PMID: 18026097
  42. Monocyte/macrophage differentiation in early multiple sclerosis lesions.
    Ann Neurol. 1995 Nov;38(5):788-96 PMID: 7486871
  43. Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration.
    J Neurosci. 2003 Oct 29;23(30):9824-32 PMID: 14586011
  44. Microgliosis: the questions shape the answers.
    Nat Neurosci. 2007 Dec;10(12):1507-9 PMID: 18043584
  45. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis.
    Nature. 2007 Apr 26;446(7139):1091-5 PMID: 17410128
  46. Interleukin-1beta promotes repair of the CNS.
    J Neurosci. 2001 Sep 15;21(18):7046-52 PMID: 11549714
  47. Why is Wallerian degeneration in the CNS so slow?
    Annu Rev Neurosci. 2007;30:153-79 PMID: 17506644
  48. Identification of Tim4 as a phosphatidylserine receptor.
    Nature. 2007 Nov 15;450(7168):435-9 PMID: 17960135
  49. Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis.
    Eur J Immunol. 2007 May;37(5):1290-301 PMID: 17407101
  50. Inflammation in the nervous system.
    Curr Opin Neurobiol. 1995 Oct;5(5):636-41 PMID: 8580715
  51. Enhancing central nervous system remyelination in multiple sclerosis.
    Neuron. 2005 Oct 6;48(1):9-12 PMID: 16202704
  52. Invasion of hematopoietic cells into the brain of amyloid precursor protein transgenic mice.
    J Neurosci. 2005 Nov 30;25(48):11125-32 PMID: 16319312
  53. Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression.
    Neurobiol Dis. 2005 Feb;18(1):166-75 PMID: 15649707
  54. ATP mediates rapid microglial response to local brain injury in vivo.
    Nat Neurosci. 2005 Jun;8(6):752-8 PMID: 15895084
  55. Engulfing action of glial cells is required for programmed axon pruning during Drosophila metamorphosis.
    Curr Biol. 2004 Apr 20;14(8):668-77 PMID: 15084281
  56. Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis.
    J Neurosci Res. 1994 Jul 1;38(4):365-75 PMID: 7932870
  57. Demyelination and remyelination of the caudal cerebellar peduncle of adult rats following stereotaxic injections of lysolecithin, ethidium bromide, and complement/anti-galactocerebroside: a comparative study.
    Glia. 1999 Feb 1;25(3):216-28 PMID: 9932868
  58. Nogo and axon regeneration.
    Curr Opin Neurobiol. 2004 Feb;14(1):118-24 PMID: 15018947
  59. "Recruitment signals" from apoptotic cells: invitation to a quiet meal.
    Cell. 2003 Jun 27;113(7):817-20 PMID: 12837239
  60. Characterization and distribution of phagocytic macrophages in multiple sclerosis plaques.
    Neuropathol Appl Neurobiol. 1993 Jun;19(3):214-23 PMID: 7689189
  61. The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation.
    J Neurosci. 2002 Apr 1;22(7):2451-9 PMID: 11923409
  62. Increasing local levels of IGF-I mRNA expression using adenoviral vectors does not alter oligodendrocyte remyelination in the CNS of aged rats.
    Mol Cell Neurosci. 2002 Jan;19(1):32-42 PMID: 11817896
  63. Peripheral nerve-stimulated macrophages simulate a peripheral nerve-like regenerative response in rat transected optic nerve.
    Glia. 1998 Nov;24(3):329-37 PMID: 9775984
  64. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease.
    Nat Med. 2007 Apr;13(4):432-8 PMID: 17351623
  65. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model.
    Neuron. 2007 Feb 1;53(3):337-51 PMID: 17270732
  66. Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis.
    Neuron. 2006 Jun 15;50(6):855-67 PMID: 16772168
  67. Essential role of the microglial triggering receptor expressed on myeloid cells-2 (TREM2) for central nervous tissue immune homeostasis.
    J Neuroimmunol. 2007 Mar;184(1-2):92-9 PMID: 17239445
  68. TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination.
    Nat Neurosci. 2001 Nov;4(11):1116-22 PMID: 11600888
  69. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells.
    Mol Cell Neurosci. 2006 Jan;31(1):149-60 PMID: 16297637
  70. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.
    Science. 2005 May 27;308(5726):1314-8 PMID: 15831717
  71. The P2Y12 receptor regulates microglial activation by extracellular nucleotides.
    Nat Neurosci. 2006 Dec;9(12):1512-9 PMID: 17115040
Article Info
Journal
Brain : a journal of neurology
Abbr.
Brain
ISSN
1460-2156
DOI
10.1093/brain/awn109
Email
hneuman1@uni-bonn.de
Published
2009-02-00
Epub
2008-00-20
Pages
288-95
Language
English
Region
England
NLM ID
0372537
PMCID
PMC2640215
Subset
IM
Grants
Medical Research Council · G0300723 · United Kingdom
Medical Research Council · G0800784 · United Kingdom
External Links
PubMed source DOI: 10.1093/brain/awn109 PMC Full Text View journal details
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