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Microglia and neuronal cell death

  • José L. Marín-Teva (a1), Miguel A. Cuadros (a1), David Martín-Oliva (a1) and Julio Navascués (a1)

Microglia, the brain's innate immune cell type, are cells of mesodermal origin that populate the central nervous system (CNS) during development. Undifferentiated microglia, also called ameboid microglia, have the ability to proliferate, phagocytose apoptotic cells and migrate long distances toward their final destinations throughout all CNS regions, where they acquire a mature ramified morphological phenotype. Recent studies indicate that ameboid microglial cells not only have a scavenger role during development but can also promote the death of some neuronal populations. In the mature CNS, adult microglia have highly motile processes to scan their territorial domains, and they display a panoply of effects on neurons that range from sustaining their survival and differentiation contributing to their elimination. Hence, the fine tuning of these effects results in protection of the nervous tissue, whereas perturbations in the microglial response, such as the exacerbation of microglial activation or lack of microglial response, generate adverse situations for the organization and function of the CNS. This review discusses some aspects of the relationship between microglial cells and neuronal death/survival both during normal development and during the response to injury in adulthood.

Corresponding author
Correspondence should be addressed to: José L. Marín-Teva, Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, E-18071 Granada, Spain phone: +34-958-246335; +34-958-243258 email:
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J. Aarum , K. Sandberg , S.L. Haeberlein and M.A. Persson (2003) Migration and differentiation of neural precursor cells can be directed by microglia. Proceedings of the National Academy of Sciences of the U.S.A. 100, 1598315988.

L. Acarin , B. Gonzalez , B. Castellano and A.J. Castro (1996) Microglial response to N-methyl-D-aspartate-mediated excitotoxicity in the immature rat brain. Journal of Comparative Neurology 367, 361374.

F. Alliot , I. Godin and B. Pessac (1999) Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Developmental Brain Research 117, 145152.

A.V. Andjelkovic , B. Nikolic , J.S. Pachter and N. Zecevic (1998) Macrophages/microglial cells in human central nervous system during development: an immunohistochemical study. Brain Research 814, 1325.

K. Ashwell (1990) Microglia and cell death in the developing mouse cerebellum. Developmental Brain Research 55, 219230.

K. Ashwell (1991) The distribution of microglia and cell death in the fetal rat forebrain. Developmental Brain Research 58, 112.

Y.A. Barde (1989) Trophic factors and neuronal survival. Neuron 2, 15251534.

A. Bessis , C. Bechade , D. Bernard and A. Roumier (2007) Microglial control of neuronal death and synaptic properties. Glia 55, 233238.

M.E. Bianchi (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. Journal of Leukocyte Biology 81, 15.

K. Biber , H. Neumann , K. Inoue and H.W. Boddeke (2007) Neuronal ‘On’ and ‘Off’ signals control microglia. Trends in Neurosciences 30, 596602.

I. Bjelobaba , A. Parabucki , I. Lavrnja , D. Stojkov , S. Dacic , S. Pekovic (2011) Dynamic changes in the expression pattern of ecto-5′-nucleotidase in the rat model of cortical stab injury. Journal of Neuroscience Research 89, 862873.

M.L. Block and J.S. Hong (2007) Chronic microglial activation and progressive dopaminergic neurotoxicity. Biochemical Society Transactions 35, 11271132.

M.L. Block , L. Zecca and J.S. Hong (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nature Reviews Neuroscience 8, 5769.

N. Braun , C. Lenz , F. Gillardon , M. Zimmermann and H. Zimmermann (1997) Focal cerebral ischemia enhances glial expression of ecto-5′-nucleotidase. Brain Research 766, 213226.

N. Braun , J. Sevigny , S.C. Robson , K. Enjyoji , O. Guckelberger , K. Hammer (2000) Assignment of ecto-nucleoside triphosphate diphosphohydrolase-1/cd39 expression to microglia and vasculature of the brain. European Journal of Neuroscience 12, 43574366.

G.C. Brown (2010) Nitric oxide and neuronal death. Nitric Oxide 23, 153165.

G.C. Brown and J.J. Neher (2010) Inflammatory neurodegeneration and mechanisms of microglial killing of neurons. Molecular Neurobiology 41, 242247.

R.R. Buss , W. Sun and R.W. Oppenheim (2006) Adaptive roles of programmed cell death during nervous system development. Annual Reviews of Neuroscience 29, 135.

J. Calderó , N. Brunet , D. Ciutat , M. Hereu and J.E. Esquerda (2009) Development of microglia in the chick embryo spinal cord: implications in the regulation of motoneuronal survival and death. Journal of Neuroscience Research 87, 24472466.

B. Cameron and G.E. Landreth (2010) Inflammation, microglia, and Alzheimer's disease. Neurobiology of Disease 37, 503509.

W.Y. Chan , S. Kohsaka and P. Rezaie (2007) The origin and cell lineage of microglia: new concepts. Brain Research Reviews 53, 344354.

C.A. Colton (2009) Heterogeneity of microglial activation in the innate immune response in the brain. Journal of Neuroimmune Pharmacology 4, 399418.

G. Conductier , N. Blondeau , A. Guyon , J.L. Nahon and C. Rovere (2010) The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. Journal of Neuroimmunology 224, 93100.

M.A. Cuadros , C. Martin , P. Coltey , A. Almendros and J. Navascués (1993) First appearance, distribution, and origin of macrophages in the early development of the avian central nervous system. Journal of Comparative Neurology 330, 113129.

M.A. Cuadros and J. Navascués (1998) The origin and differentiation of microglial cells during development. Progress in Neurobiology 56, 173189.

M.A. Cuadros and J. Navascués (2001) Early origin and colonization of the developing central nervous system by microglial precursors. Progress in Brain Research 132, 5159.

R.A. Cunha (2005) Neuroprotection by adenosine in the brain: from A1 receptor activation to A2A receptor blockade. Purinergic Signalling 1, 111134.

I. Dalmau , J.M. Vela , B. Gonzalez and B. Castellano (1998) Expression of purine metabolism-related enzymes by microglial cells in the developing rat brain. Journal of Comparative Neurology 398, 333346.

D. Davalos , J. Grutzendler , G. Yang , J.V. Kim , Y. Zuo , S. Jung (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 8, 752758.

S. David and A. Kroner (2011) Repertoire of microglial and macrophage responses after spinal cord injury. Nature Reviews Neuroscience 12, 388399.

E.J. de la Rosa and F. de Pablo (2000) Cell death in early neural development: beyond the neurotrophic theory. Trends in Neurosciences 23, 454458.

R. De Simone , M.A. Ajmone-Cat and L. Minghetti (2004) Atypical antiinflammatory activation of microglia induced by apoptotic neurons: possible role of phosphatidylserine-phosphatidylserine receptor interaction. Molecular Neurobiology 29, 197212.

C. D'Mello , T. Le and M.G. Swain (2009) Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. Journal of Neuroscience 29, 20892102.

R. Egensperger , J. Maslim , S. Bisti , H. Hollander and J. Stone (1996) Fate of DNA from retinal cells dying during development: uptake by microglia and macroglia (Muller cells). Developmental Brain Research 97, 18.

M.R. Elliott , F.B. Chekeni , P.C. Trampont , E.R. Lazarowski , A. Kadl , S.F. Walk (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461, 282286.

V.A. Fadok , D.L. Bratton , D.M. Rose , A. Pearson , R.A. Ezekewitz and P.M. Henson (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405, 8590.

K. Farber , S. Markworth , U. Pannasch , C. Nolte , V. Prinz , G. Kronenberg (2008) The ectonucleotidase cd39/ENTPDase1 modulates purinergic-mediated microglial migration. Glia 56, 331341.

I. Ferrer , E. Bernet , E. Soriano , T. del Rio and M. Fonseca (1990) Naturally occurring cell death in the cerebral cortex of the rat and removal of dead cells by transitory phagocytes. Neuroscience 39, 451458.

B.K. Fiske and P.C. Brunjes (2000) Microglial activation in the developing rat olfactory bulb. Neuroscience 96, 807815.

D. Fitzner , M. Schnaars , D. van Rossum , G. Krishnamoorthy , P. Dibaj , M. Bakhti (2011) Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. Journal of Cell Science 124, 447458.

M.P. Flavin , G. Zhao and L.T. Ho (2000) Microglial tissue plasminogen activator (tPA) triggers neuronal apoptosis in vitro. Glia 29, 347354.

J.M. Frade and Y.A. Barde (1998) Microglia-derived nerve growth factor causes cell death in the developing retina. Neuron 20, 3541.

O. Fukui , Y. Kinugasa , A. Fukuda , H. Fukuda , E. Tskitishvili , S. Hayashi (2006) Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain. Brain Research 1121, 3545.

M. Gandelman , H. Peluffo , J.S. Beckman , P. Cassina and L. Barbeito (2010) Extracellular ATP and the P2X7 receptor in astrocyte-mediated motor neuron death: implications for amyotrophic lateral sclerosis. Journal of Neuroinflammation 7, 33.

H.M. Gao , H. Zhou , F. Zhang , B.C. Wilson , W. Kam and J.S. Hong (2011) HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. Journal of Neuroscience 31, 10811092.

J.A. García-Porrero and J.L. Ojeda (1979) Cell death and phagocytosis in the neuroepithelium of the developing retina. A TEM and SEM study. Experientia 35, 375376.

F. Ginhoux , M. Greter , M. Leboeuf , S. Nandi , P. See , S. Gokhan (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841845.

S. Gordon and P.R. Taylor (2005) Monocyte and macrophage heterogeneity. Nature Reviews Immunology 5, 953964.

M.B. Graeber , F. Lopez-Redondo , E. Ikoma , M. Ishikawa , Y. Imai , K. Nakajima (1998) The microglia/macrophage response in the neonatal rat facial nucleus following axotomy. Brain Research 813, 241253.

U.K. Hanisch (2002) Microglia as a source and target of cytokines. Glia 40, 140155.

U.K. Hanisch and H. Kettenmann (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nature Neuroscience 10, 13871394.

A.J. Hao , S.T. Dheen and E.A. Ling (2001) Response of amoeboid microglia/brain macrophages in fetal rat brain exposed to a teratogen. Journal of Neuroscience Research 64, 7993.

S.E. Haynes , G. Hollopeter , G. Yang , D. Kurpius , M.E. Dailey , W.B. Gan (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nature Neuroscience 9, 15121519.

C.J. Henry , Y. Huang , A.M. Wynne and J.P. Godbout (2009) Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1β and anti-inflammatory IL-10 cytokines. Brain Behavior and Immunity 23, 309317.

P. Herbomel , B. Thisse and C. Thisse (2001) Zebrafish early macrophages colonize cephalic mesenchyme and developing brain, retina, and epidermis through a M-CSF receptor-dependent invasive process. Developmental Biology 238, 274288.

D.J. Hoeppner , M.O. Hengartner and R. Schnabel (2001) Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans. Nature 412, 202206.

M. Hristova , D. Cuthill , V. Zbarsky , A. Acosta-Saltos , A. Wallace , K. Blight (2010) Activation and deactivation of periventricular white matter phagocytes during postnatal mouse development. Glia 58, 1128.

C.L. Hsieh , M. Koike , S.C. Spusta , E.C. Niemi , M. Yenari , M.C. Nakamura (2009) A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. Journal of Neurochemistry 109, 11441156.

D.A. Hume , V.H. Perry and S. Gordon (1983) Immunohistochemical localization of a macrophage-specific antigen in developing mouse retina: phagocytosis of dying neurons and differentiation of microglial cells to form a regular array in the plexiform layers. Journal of Cell Biology 97, 253257.

J. Hur , P. Lee , M.J. Kim , Y. Kim and Y.W. Cho (2010) Ischemia-activated microglia induces neuronal injury via activation of gp91phox NADPH oxidase. Biochemical and Biophysical Research Communications 391, 15261530.

S.D. Hurley , S.A. Walter , S.L. Semple-Rowland and W.J. Streit (1999) Cytokine transcripts expressed by microglia in vitro are not expressed by ameboid microglia of the developing rat central nervous system. Glia 25, 304309.

H. Ilieva , M. Polymenidou and D.W. Cleveland (2009) Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. Journal of Cell Biology 187, 761772.

F. Imai , H. Suzuki , J. Oda , T. Ninomiya , K. Ono , H. Sano (2007) Neuroprotective effect of exogenous microglia in global brain ischemia. Journal of Cerebral Blood Flow and Metabolism 27, 488500.

S. Jung , J. Aliberti , P. Graemmel , M.J. Sunshine , G.W. Kreutzberg , A. Sher (2000) Analysis of fractalkine receptor CX3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Molecular and Cellular Biology 20, 41064114.

M. Kálmán (1989) Dead cells can be phagocytosed by any neighboring cell in early developing rat brain. International Journal of Neuroscience 46, 139145.

K. Kawahara , A. Yoshida , K. Koga , S. Yokoo , A. Kuniyasu , T. Gotoh (2009) Marked induction of inducible nitric oxide synthase and tumor necrosis factor-alpha in rat CD40+ microglia by comparison to CD40- microglia. Journal of Neuroimmunology 208, 7079.

H. Kettenmann , U.K. Hanisch , M. Noda and A. Verkhratsky (2011) Physiology of microglia. Physiological Reviews 91, 461553.

S. Koizumi , Y. Shigemoto-Mogami , K. Nasu-Tada , Y. Shinozaki , K. Ohsawa , M. Tsuda (2007) UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446, 10911095.

N.V. Konduru , Y.Y. Tyurina , W. Feng , L.V. Basova , N.A. Belikova , H. Bayir (2009) Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo. PLoS ONE 4, e4398.

H. Kono and K.L. Rock (2008) How dying cells alert the immune system to danger. Nature Reviews Immunology 8, 279289.

G. W. Kreutzberg (1996) Microglia: a sensor for pathological events in the CNS. Trends in Neurosciences 19, 312318.

C.Y. Kuan , K.A. Roth , R.A. Flavell and P. Rakic (2000) Mechanisms of programmed cell death in the developing brain. Trends in Neurosciences 23, 291297.

H. Kumar , T. Kawai and S. Akira (2011) Pathogen recognition by the innate immune system. International Reviews of Immunology 30, 1634.

A.Y. Lai and K.G. Todd (2008) Differential regulation of trophic and proinflammatory microglial effectors is dependent on severity of neuronal injury. Glia 56, 259270.

M. Lalancette-Hebert , G. Gowing , A. Simard , Y.C. Weng and J. Kriz (2007) Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. Journal of Neuroscience 27, 25962605.

K. Lauber , S.G. Blumenthal , M. Waibel and S. Wesselborg (2004) Clearance of apoptotic cells: getting rid of the corpses. Molecular Cell 14, 277287.

K. Lauber , E. Bohn , S.M. Krober , Y.J. Xiao , S.G. Blumenthal , R.K. Lindemann (2003) Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113, 717730.

K.J. Liang , J.E. Lee , Y.D. Wang , W. Ma , A.M. Fontainhas , R.N. Fariss (2009) Regulation of dynamic behavior of retinal microglia by CX3CR1 signaling. Investigative Ophthalmology and Visual Science 50, 44444451.

A.M. Lichanska and D.A. Hume (2000) Origins and functions of phagocytes in the embryo. Experimental Hematology 28, 601611.

M. Liu and G. Bing (2011) Lipopolysaccharide animal models for Parkinson's disease. Parkinson's Disease 2011, 327089, doi: 10.4061/2011/327089.

Z.G. Liu , H. Hsu , D.V. Goeddel and M. Karin (1996) Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappaB activation prevents cell death. Cell 87, 565576.

D.J. Loane and K.R. Byrnes (2010) Role of microglia in neurotrauma. Neurotherapeutics 7, 366377.

M.E. Lull and M.L. Block (2010) Microglial activation and chronic neurodegeneration. Neurotherapeutics 7, 354365.

A. Lyons , E.J. Downer , S. Crotty , Y.M. Nolan , K.H. Mills and M.A. Lynch (2007) CD200 ligand-receptor interaction modulates microglial activation in vivo and in vitro: a role for IL-4. Journal of Neuroscience 27, 83098313.

M. Mallat , J.L. Marín-Teva and C. Cheret (2005) Phagocytosis in the developing CNS: more than clearing the corpses. Current Opinion in Neurobiology 15, 101107.

J.L. Marín-Teva , M.A. Cuadros , R. Calvente , A. Almendros and J. Navascués (1999) Naturally occurring cell death and migration of microglial precursors in the quail retina during normal development. Journal of Comparative Neurology 412, 255275.

J.L. Marín-Teva , I. Dusart , C. Colin , A. Gervais , N. van Rooijen and M. Mallat (2004) Microglia promote the death of developing Purkinje cells. Neuron 41, 535547.

D. Mevorach , J.O. Mascarenhas , D. Gershov and K.B. Elkon (1998) Complement-dependent clearance of apoptotic cells by human macrophages. Journal of Experimental Medicine 188, 23132320.

M. Mizutani , P.A. Pino , N. Saederup , I.F. Charo , R.M. Ransohoff and A.E. Cardona (2012) The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. Journal of Immunology 188, 2936.

S.C. Morgan , D.L. Taylor and J.M. Pocock (2004) Microglia release activators of neuronal proliferation mediated by activation of mitogen-activated protein kinase, phosphatidylinositol-3-kinase/Akt and delta-Notch signalling cascades. Journal of Neurochemistry 90, 89101.

T. Morioka and W.J. Streit (1991) Expression of immunomolecules on microglial cells following neonatal sciatic nerve axotomy. Journal of Neuroimmunology 35, 2130.

A. Moujahid , J. Navascués , J.L. Marín-Teva and M.A. Cuadros (1996) Macrophages during avian optic nerve development: relationship to cell death and differentiation into microglia. Anatomy and Embryology 193, 131144.

M.P. Mount , A. Lira , D. Grimes , P.D. Smith , S. Faucher , R. Slack (2007) Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons. Journal of Neuroscience 27, 33283337.

K. Nakajima , S. Honda , Y. Tohyama , Y. Imai , S. Kohsaka and T. Kurihara (2001) Neurotrophin secretion from cultured microglia. Journal of Neuroscience Research 65, 322331.

T. Nakazawa , T. Hisatomi , C. Nakazawa , K. Noda , K. Maruyama , H. She (2007) Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis. Proceedings of the National Academy of Sciences of the U.S.A. 104, 24252430.

J. Navascués , A. Moujahid , A. Almendros , J.L. Marín-Teva and M.A. Cuadros (1995) Origin of microglia in the quail retina: central-to-peripheral and vitreal-to-scleral migration of microglial precursors during development. Journal of Comparative Neurology 354, 209228.

N. Nedeljkovic , I. Bjelobaba , S. Subasic , I. Lavrnja , S. Pekovic , D. Stojkov (2006) Up-regulation of ectonucleotidase activity after cortical stab injury in rats. Cell Biology International 30, 541546.

J.J. Neher , U. Neniskyte , J.W. Zhao , A. Bal-Price , A.M. Tolkovsky and G.C. Brown (2011) Inhibition of microglial phagocytosis is sufficient to prevent inflammatory neuronal death. Journal of Immunology 186, 49734983.

U. Neniskyte , J.J. Neher and G.C. Brown (2011) Neuronal death induced by nanomolar amyloid β is mediated by primary phagocytosis of neurons by microglia. Journal of Biological Chemistry 286, 3990439913.

H. Neumann , M.R. Kotter and R.J. Franklin (2009) Debris clearance by microglia: an essential link between degeneration and regeneration. Brain 132, 288295.

A. Nimmerjahn , F. Kirchhoff and F. Helmchen (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 13141318.

M. Noda , Y. Doi , J. Liang , J. Kawanokuchi , Y. Sonobe , H. Takeuchi (2011) Fractalkine attenuates excito-neurotoxicity via microglial clearance of damaged neurons and antioxidant enzyme heme oxygenase-1 expression. Journal of Biological Chemistry 286, 23082319.

T.M. O'Connor and C.R. Wyttenbach (1974) Cell death in the embryonic chick spinal cord. Journal of Cell Biology 60, 448459.

K. Ohsawa and S. Kohsaka (2011) Dynamic motility of microglia: purinergic modulation of microglial movement in the normal and pathological brain. Glia 59, 17931799.

M. Olah , S. Amor , N. Brouwer , J. Vinet , B. Eggen , K. Biber (2012) Identification of a microglia phenotype supportive of remyelination. Glia 60, 306321.

M. Olah , K. Biber , J. Vinet and H.W.G.M. Boddeke (2011) Microglia phenotype diversity. CNS and Neurological Disorders-Drug Targets 10, 108118.

R.W. Oppenheim (1989) The neurotrophic theory and naturally occurring motoneuron death. Trends in Neurosciences 12, 252255.

R.W. Oppenheim (1991) Cell death during development of the nervous system. Annual Review of Neuroscience 14, 453501.

K.W. Park , D.Y. Lee , E.H. Joe , S.U. Kim and B.K. Jin (2005) Neuroprotective role of microglia expressing interleukin-4. Journal of Neuroscience Research 81, 397402.

R. Parnaik , M.C. Raff and J. Scholes (2000) Differences between the clearance of apoptotic cells by professional and non-professional phagocytes. Current Biology 10, 857860.

H.E. Pearson , B.R. Payne and T.J. Cunningham (1993) Microglial invasion and activation in response to naturally occurring neuronal degeneration in the ganglion cell layer of the postnatal cat retina. Developmental Brain Research 76, 249255.

F. Peri and C. Nüsslein-Volhard (2008) Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo. Cell 133, 916927.

V.H. Perry and S. Gordon (1991) Macrophages and the nervous system. International Review of Cytology 125, 203244.

V.H. Perry , D.A. Hume and S. Gordon (1985) Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15, 313326.

V.H. Perry , J.A. Nicoll and C. Holmes (2010) Microglia in neurodegenerative disease. Nature Reviews Neurology 6, 193201.

C. Peter , M. Waibel , C.G. Radu , L.V. Yang , O.N. Witte , K. Schulze-Osthoff (2008) Migration to apoptotic ‘find-me’ signals is mediated via the phagocyte receptor G2A. Journal of Biological Chemistry 283, 52965305.

D. Piani , K. Frei , K.Q. Do , M. Cuenod and A. Fontana (1991) Murine brain macrophages induced NMDA receptor mediated neurotoxicity in vitro by secreting glutamate. Neuroscience Letters 133, 159162.

A.M. Piccinini and K.S. Midwood (2010) DAMPening inflammation by modulating TLR signalling. Mediators of Inflammation 2010, 672395, doi:10.1155/2010/672395.

E. Polazzi , L.E. Altamira , S. Eleuteri , R. Barbaro , C. Casadio , A. Contestabile (2009) Neuroprotection of microglial conditioned medium on 6-hydroxydopamine-induced neuronal death: role of transforming growth factor beta-2. Journal of Neurochemistry 110, 545556.

M. Prinz and A. Mildner (2011) Microglia in the CNS: immigrants from another world. Glia 59, 177187.

M. Prinz , J. Priller , S.S. Sisodia and R.M. Ransohoff (2011) Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nature Neuroscience 13, 12271235.

L. Qin , Y. Liu , T. Wang , S.J. Wei , M.L. Block , B. Wilson (2004) NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. Journal of Biological Chemistry 279, 14151421.

M.C. Raff , B.A. Barres , J.F. Burne , H.S. Coles , Y. Ishizaki and M.D. Jacobson (1993) Programmed cell death and the control of cell survival: lessons from the nervous system. Science 262, 695700.

G. Raivich , M. Bohatschek , C.U. Kloss , A. Werner , L.L. Jones and G.W. Kreutzberg (1999) Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function. Brain Research Reviews 30, 77105.

S. Rakic and N. Zecevic (2000) Programmed cell death in the developing human telencephalon. European Journal of Neuroscience 12, 27212734.

R.M. Ransohoff and V.H. Perry (2009) Microglial physiology: unique stimuli, specialized responses. Annual Review of Immunology 27, 119145.

K.S. Ravichandran (2010) Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. Journal of Experimental Medicine 207, 18071817.

P.W. Reddien , S. Cameron and H.R. Horvitz (2001) Phagocytosis promotes programmed cell death in C. elegans. Nature 412, 198202.

P. Rezaie and D. Male (1999) Colonisation of the developing human brain and spinal cord by microglia: a review. Microscopy Research and Technique 45, 359382.

C.E. Ribak , L.A. Shapiro , Z.D. Perez and I. Spigelman (2009) Microglia-associated granule cell death in the normal adult dentate gyrus. Brain Structure and Function 214, 2535.

C. Rigato , R. Buckinx , H. Le-Corronc , J.M. Rigo and P. Legendre (2011) Pattern of invasion of the embryonic mouse spinal cord by microglial cells at the time of the onset of functional neuronal networks. Glia 59, 675695.

M. Rutar , R. Natoli , K. Valter and J.M. Provis (2011) Early focal expression of the chemokine Ccl2 by Muller cells during exposure to damage-inducing bright continuous light. Investigative Ophthalmology and Visual Science 52, 23792388.

J.K. Ryu , J. Kim , S.H. Choi , Y.J. Oh , Y.B. Lee , S.U. Kim (2002) ATP-induced in vivo neurotoxicity in the rat striatum via P2 receptors. Neuroreport 13, 16111615.

K. Saijo and C.K. Glass (2011) Microglial cell origin and phenotypes in health and disease. Nature Reviews Immunology 11, 775787.

A.M. Sánchez-López , M.A. Cuadros , R. Calvente , M. Tassi , J.L. Marín-Teva and J. Navascués (2005) Activation of immature microglia in response to stab wound in embryonic quail retina. Journal of Comparative Neurology 492, 2033.

A.M. Santos , R. Calvente , M. Tassi , M.C. Carrasco , D. Martín-Oliva , J.L. Marín-Teva (2008) Embryonic and postnatal development of microglial cells in the mouse retina. Journal of Comparative Neurology 506, 224239.

J. Savill and V. Fadok (2000) Corpse clearance defines the meaning of cell death. Nature 407, 784788.

M. Sawada , H. Sawada and T. Nagatsu (2008) Effects of aging on neuroprotective and neurotoxic properties of microglia in neurodegenerative diseases. Neurodegenerative Diseases 5, 254256.

M. Schilling , J.K. Strecker , W.R. Schabitz , E.B. Ringelstein and R. Kiefer (2009) Effects of monocyte chemoattractant protein 1 on blood-borne cell recruitment after transient focal cerebral ischemia in mice. Neuroscience 161, 806812.

T. Schlegelmilch , K. Henke and F. Peri (2011) Microglia in the developing brain: from immunity to behaviour. Current Opinion in Neurobiology 21, 510.

F. Sedel , C. Bechade , S. Vyas and A. Triller (2004) Macrophage-derived tumor necrosis factor α, an early developmental signal for motoneuron death. Journal of Neuroscience 24, 22362246.

S. Shan , T. Hong-Min , F. Yi , G. Jun-Peng , F. Yue , T. Yan-Hong (2011) New evidences for fractalkine/CX3CL1 involved in substantia nigral microglial activation and behavioral changes in a rat model of Parkinson's disease. Neurobiology of Aging 32, 443458.

A. Sierra , J.M. Encinas , J.J. Deudero , J.H. Chancey , G. Enikolopov , L.S. Overstreet-Wadiche (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7, 483495.

A.R. Simard and S. Rivest (2007) Neuroprotective effects of resident microglia following acute brain injury. Journal of Comparative Neurology 504, 716729.

V. Sivakumar , W.S. Foulds , C.D. Luu , E.A. Ling and C. Kaur (2011) Retinal ganglion cell death is induced by microglia derived pro-inflammatory cytokines in the hypoxic neonatal retina. Journal of Pathology 224, 245260.

J.A. Smith , A. Das , S.K. Ray and N.L. Banik (2012) Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Research Bulletin 87, 1020.

W.D. Snider (1994) Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77, 627638.

S.P. Sorokin , R.F. Hoyt Jr., D.G. Blunt and N.A. McNelly (1992) Macrophage development: II. Early ontogeny of macrophage populations in brain, liver, and lungs of rat embryos as revealed by a lectin marker. Anatomical Record 232, 527550.

T.W. Stone (2002) Purines and neuroprotection. Advances in Experimental Medicine and Biology 513, 249280.

W.J. Streit (2001) Microglia and macrophages in the developing CNS. Neurotoxicology 22, 619624.

K. Takahashi , C.D. Rochford and H. Neumann (2005) Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. Journal of Experimental Medicine 201, 647657.

S. Takahashi , T. Ohshima , M. Hirasawa , T.K. Pareek , T.H. Bugge , A. Morozov (2010) Conditional deletion of neuronal cyclin-dependent kinase 5 in developing forebrain results in microglial activation and neurodegeneration. American Journal of Pathology 176, 320329.

M.G. Tansey and M.S. Goldberg (2010) Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention. Neurobiology of Disease 37, 510518.

S. Taylor , C.J. Calder , J. Albon , J.T. Erichsen , M.E. Boulton and J.E. Morgan (2011) Involvement of the CD200 receptor complex in microglia activation in experimental glaucoma. Experimental Eye Research 92, 338343.

S. Thanos (1991) The relationship of microglial cells to dying neurons during natural neuronal cell death and axotomy-induced degeneration of the rat retina. European Journal of Neuroscience 3, 11891207.

C. Thery , B. Chamak and M. Mallat (1991) Cytotoxic effect of brain macrophages on developing neurons. European Journal of Neuroscience 3, 11551164.

L.A. Truman , C.A. Ford , M. Pasikowska , J.D. Pound , S.J. Wilkinson , I.E. Dumitriu , (2008) CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis. Blood 112, 50265036.

M.B. Upender and J.R. Naegele (1999) Activation of microglia during developmentally regulated cell death in the cerebral cortex. Developmental Neuroscience 21, 491505.

A.I. Valenciano , P. Boya and E.J. de la Rosa (2009) Early neural cell death: numbers and cues from the developing neuroretina. International Journal of Developmental Biology 53, 15151528.

D. van Rossum and U.K. Hanisch (2004) Microglia. Metabolic Brain Disease 19, 393411.

R. von Bernhardi , J.E. Tichauer and J. Eugenin (2010) Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders. Journal of Neurochemistry 112, 10991114.

H. Wake , A.J. Moorhouse , S. Jinno , S. Kohsaka and J. Nabekura (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. Journal of Neuroscience 29, 39743980.

S. Wakselman , C. Bechade , A. Roumier , D. Bernard , A. Triller and A. Bessis (2008) Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor. Journal of Neuroscience 28, 81388143.

L. Walter and H. Neumann (2009) Role of microglia in neuronal degeneration and regeneration. Seminars in Immunopathology 31, 513525.

N.M. Walton , B.M. Sutter , E.D. Laywell , L.H. Levkoff , S.M. Kearns , G.P. Marshall 2nd, (2006) Microglia instruct subventricular zone neurogenesis. Glia 54, 815825.

R. Wei and C.M. Lin (2009) Strain-dependent inflammatory responsiveness of rat microglial cells. Journal of Neuroimmunology 211, 2338.

M.R. Wink , E. Braganhol , A.S. Tamajusuku , G. Lenz , L.F. Zerbini , T.A. Libermann , (2006) Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) is the dominant ectonucleotidase expressed by rat astrocytes. Neuroscience 138, 421432.

X. Xiong , G.E. Barreto , L. Xu , Y.B. Ouyang , X. Xie and R.G. Giffard (2011) Increased brain injury and worsened neurological outcome in interleukin-4 knockout mice after transient focal cerebral ischemia. Stroke 42, 20262032.

W. Yeo and J. Gautier (2004) Early neural cell death: dying to become neurons. Developmental Biology 274, 233244.

J. Yuan and B.A. Yankner (2000) Apoptosis in the nervous system. Nature 407, 802809.

H. Zimmermann and N. Braun (1996) Extracellular metabolism of nucleotides in the nervous system. Journal of Autonomic Pharmacology 16, 397400.

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Neuron Glia Biology
  • ISSN: 1740-925X
  • EISSN: 1741-0533
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