期刊论文详细信息
Translational Neurodegeneration
The changing phenotype of microglia from homeostasis to disease
Sheng-Di Chen1  Xiao-Guang Luo2 
[1] Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiao Tong University, Shanghai, 200025, China;Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, 110001, China
关键词: Crosstalk;    Senescence;    Phenotypes;    Neuroprotection;    Microglia;   
Others  :  838990
DOI  :  10.1186/2047-9158-1-9
 received in 2012-01-01, accepted in 2012-04-24,  发布年份 2012
PDF
【 摘 要 】

It has been nearly a century since the early description of microglia by Rio-Hortega; since then many more biological and pathological features of microglia have been recognized. Today, microglia are generally considered to be beneficial to homeostasis at the resting state through their abilities to survey the environment and phagocytose debris. However, when activated microglia assume diverse phenotypes ranging from fully inflamed, which involves the release of many pro-inflammatory cytokines, to alternatively activated, releasing anti-inflammatory cytokines or neurotrophins, the consequences to neurons can range from detrimental to supportive. Due to the different experimental sets and conditions, contradictory results have been obtained regarding the controversial question of whether microglia are “good” or “bad.” While it is well understood that the dual roles of activated microglia depend on specific situations, the underlying mechanisms have remained largely unclear, and the interpretation of certain findings related to diverse microglial phenotypes continues to be problematic. In this review we discuss the functions of microglia in neuronal survival and neurogenesis, the crosstalk between microglia and surrounding cells, and the potential factors that could influence the eventual manifestation of microglia.

【 授权许可】

   
2012 Luo and Chen; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140716032120376.pdf 615KB PDF download
Figure 1. 50KB Image download
【 图 表 】

Figure 1.

【 参考文献 】
  • [1]Farber K, Kettenmann H: Purinergic signaling and microglia. Pflugers Arch 2006, 452:615-621.
  • [2]Hanisch UK, Kettenmann H: Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007, 10:1387-1394.
  • [3]Kettenmann H, Hanisch UK, Noda M, Verkhratsky A: Physiology of microglia. Physiol Rev 2011, 91:461-553.
  • [4]Kettenmann H, Banati R, Walz W: Electrophysiological behavior of microglia. Glia 1993, 7:93-101.
  • [5]Noda M, Kettenmann H, Wada K: Anti-inflammatory effects of kinins via microglia in the central nervous system. Biol Chem 2006, 387:167-171.
  • [6]Pocock JM, Kettenmann H: Neurotransmitter receptors on microglia. Trends Neurosci 2007, 30:527-535.
  • [7]Skoff RP: The fine structure of pulse labeled (3-H-thymidine cells) in degenerating rat optic nerve. J Comp Neurol 1975, 161:595-611.
  • [8]Kitamura T, Miyake T, Fujita S: Genesis of resting microglia in the gray matter of mouse hippocampus. J Comp Neurol 1984, 226:421-433.
  • [9]Alliot F, Lecain E, Grima B, Pessac B: Microglial progenitors with a high proliferative potential in the embryonic and adult mouse brain. Proc Natl Acad Sci U S A 1991, 88:1541-1545.
  • [10]Priller J, Flugel A, Wehner T, Boentert M, Haas CA, Prinz M, Fernandez-Klett F, Prass K, Bechmann I, de Boer BA, et al.: Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat Med 2001, 7:1356-1361.
  • [11]Ritter MR, Banin E, Moreno SK, Aguilar E, Dorrell MI, Friedlander M: Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy. J Clin Invest 2006, 116:3266-3276.
  • [12]Ling EA, Penney D, Leblond CP: Use of carbon labeling to demonstrate the role of blood monocytes as precursors of the 'ameboid cells’ present in the corpus callosum of postnatal rats. J Comp Neurol 1980, 193:631-657.
  • [13]Davoust N, Vuaillat C, Cavillon G, Domenget C, Hatterer E, Bernard A, Dumontel C, Jurdic P, Malcus C, Confavreux C, et al.: Bone marrow CD34+/B220+ progenitors target the inflamed brain and display in vitro differentiation potential toward microglia. Faseb J 2006, 20:2081-2092.
  • [14]Schmitz G, Leuthauser-Jaschinski K, Orso E: Are circulating monocytes as microglia orthologues appropriate biomarker targets for neuronal diseases? Cent Nerv Syst Agents Med Chem 2009, 9:307-330.
  • [15]Djukic M, Mildner A, Schmidt H, Czesnik D, Bruck W, Priller J, Nau R, Prinz M: Circulating monocytes engraft in the brain, differentiate into microglia and contribute to the pathology following meningitis in mice. Brain 2006, 129:2394-2403.
  • [16]Templeton SP, Kim TS, O’Malley K, Perlman S: Maturation and localization of macrophages and microglia during infection with a neurotropic murine coronavirus. Brain Pathol 2008, 18:40-51.
  • [17]Liu M, Eguchi N, Yamasaki Y, Urade Y, Hattori N, Urabe T: Focal cerebral ischemia/reperfusion injury in mice induces hematopoietic prostaglandin D synthase in microglia and macrophages. Neuroscience 2007, 145:520-529.
  • [18]Luo X, Carlson KA, Wojna V, Mayo R, Biskup TM, Stoner J, Anderson J, Gendelman HE, Melendez LM: Macrophage proteomic fingerprinting predicts HIV-1-associated cognitive impairment. Neurology 2003, 60:1931-1937.
  • [19]Balasubramaniam B, Carter DA, Mayer EJ, Dick AD: Microglia derived IL-6 suppresses neurosphere generation from adult human retinal cell suspensions. Exp Eye Res 2009, 89:757-766.
  • [20]Dheen ST, Jun Y, Yan Z, Tay SS, Ling EA: Retinoic acid inhibits expression of TNF-alpha and iNOS in activated rat microglia. Glia 2005, 50:21-31.
  • [21]Bi XL, Yang JY, Dong YX, Wang JM, Cui YH, Ikeshima T, Zhao YQ, Wu CF: Resveratrol inhibits nitric oxide and TNF-alpha production by lipopolysaccharide-activated microglia. Int Immunopharmacol 2005, 5:185-193.
  • [22]Moss DW, Bates TE: Activation of murine microglial cell lines by lipopolysaccharide and interferon-gamma causes NO-mediated decreases in mitochondrial and cellular function. Eur J Neurosci 2001, 13:529-538.
  • [23]Liu B, Gao HM, Wang JY, Jeohn GH, Cooper CL, Hong JS: Role of nitric oxide in inflammation-mediated neurodegeneration. Ann N Y Acad Sci 2002, 962:318-331.
  • [24]Colton CA, Gilbert DL: Production of superoxide anions by a CNS macrophage, the microglia. FEBS Lett 1987, 223:284-288.
  • [25]Mao H, Liu B: Synergistic microglial reactive oxygen species generation induced by pesticides lindane and dieldrin. Neuroreport 2008, 19:1317-1320.
  • [26]Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB: In-vivo measurement of activated microglia in dementia. Lancet 2001, 358:461-467.
  • [27]McGeer PL, Itagaki S, Tago H, McGeer EG: Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 1987, 79:195-200.
  • [28]Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y: Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol 2003, 106:518-526.
  • [29]Lawson LJ, Perry VH, Dri P, Gordon S: Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 1990, 39:151-170.
  • [30]Loeffler DA, DeMaggio AJ, Juneau PL, Havaich MK, LeWitt PA: Effects of enhanced striatal dopamine turnover in vivo on glutathione oxidation. Clin Neuropharmacol 1994, 17:370-379.
  • [31]Castano A, Herrera AJ, Cano J, Machado A: Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem 1998, 70:1584-1592.
  • [32]Liu B, Jiang JW, Wilson BC, Du L, Yang SN, Wang JY, Wu GC, Cao XD, Hong JS: Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther 2000, 295:125-132.
  • [33]Lu X, Bing G, Hagg T: Naloxone prevents microglia-induced degeneration of dopaminergic substantia nigra neurons in adult rats. Neuroscience 2000, 97:285-291.
  • [34]Cartier L, Hartley O, Dubois-Dauphin M, Krause KH: Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 2005, 48:16-42.
  • [35]Duan Y, Sahley CL, Muller KJ: ATP and NO dually control migration of microglia to nerve lesions. Dev Neurobiol 2009, 69:60-72.
  • [36]Farinas I, Cano-Jaimez M, Bellmunt E, Soriano M: Regulation of neurogenesis by neurotrophins in developing spinal sensory ganglia. Brain Res Bull 2002, 57:809-816.
  • [37]Markus A, Patel TD, Snider WD: Neurotrophic factors and axonal growth. Curr Opin Neurobiol 2002, 12:523-531.
  • [38]Oppenheim RW, Prevette D, Tytell M, Homma S: Naturally occurring and induced neuronal death in the chick embryo in vivo requires protein and RNA synthesis: evidence for the role of cell death genes. Dev Biol 1990, 138:104-113.
  • [39]Miller FD, Kaplan DR: Neurotrophin signalling pathways regulating neuronal apoptosis. Cell Mol Life Sci 2001, 58:1045-1053.
  • [40]Nimmerjahn A, Kirchhoff F, Helmchen F: Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005, 308:1314-1318.
  • [41]Battisti WP, Wang J, Bozek K, Murray M: 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, 354:306-320.
  • [42]Hao HP, Doh-Ura K, Nakanishi H: Impairment of microglial responses to facial nerve axotomy in cathepsin S-deficient mice. J Neurosci Res 2007, 85:2196-2206.
  • [43]Sawada H, Hishida R, Hirata Y, Ono K, Suzuki H, Muramatsu S, Nakano I, Nagatsu T, Sawada M: Activated microglia affect the nigro-striatal dopamine neurons differently in neonatal and aged mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurosci Res 2007, 85:1752-1761.
  • [44]Shaked I, Tchoresh D, Gersner R, Meiri G, Mordechai S, Xiao X, Hart RP, Schwartz M: Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators. J Neurochem 2005, 92:997-1009.
  • [45]Bruccoleri A, Harry GJ: Chemical-induced hippocampal neurodegeneration and elevations in TNFalpha, TNFbeta, IL-1alpha, IP-10, and MCP-1 mRNA in osteopetrotic (op/op) mice. J Neurosci Res 2000, 62:146-155.
  • [46]Lalancette-Hebert M, Gowing G, Simard A, Weng YC, Kriz J: Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J Neurosci 2007, 27:2596-2605.
  • [47]Lambertsen KL, Clausen BH, Babcock AA, Gregersen R, Fenger C, Nielsen HH, Haugaard LS, Wirenfeldt M, Nielsen M, Dagnaes-Hansen F, et al.: Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. J Neurosci 2009, 29:1319-1330.
  • [48]Napoli I, Neumann H: Protective effects of microglia in multiple sclerosis. Exp Neurol 2010, 225:24-28.
  • [49]Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, et al.: Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 1998, 4:814-821.
  • [50]Rabchevsky AG, Streit WJ: Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res 1997, 47:34-48.
  • [51]Morigiwa K, Quan M, Murakami M, Yamashita M, Fukuda Y: P2 Purinoceptor expression and functional changes of hypoxia-activated cultured rat retinal microglia. Neurosci Lett 2000, 282:153-156.
  • [52]Bosco A, Steele MR, Vetter ML: Early microglia activation in a mouse model of chronic glaucoma. J Comp Neurol 2011, 519:599-620.
  • [53]Hur J, Lee P, Kim MJ, Kim Y, Cho YW: Ischemia-activated microglia induces neuronal injury via activation of gp91phox NADPH oxidase. Biochem Biophys Res Commun 2010, 391:1526-1530.
  • [54]Maeda M, Tsuda M, Tozaki-Saitoh H, Inoue K, Kiyama H: Nerve injury-activated microglia engulf myelinated axons in a P2Y12 signaling-dependent manner in the dorsal horn. Glia 2010, 58:1838-1846.
  • [55]Lee EJ, Woo MS, Moon PG, Baek MC, Choi IY, Kim WK, Junn E, Kim HS: Alpha-synuclein activates microglia by inducing the expressions of matrix metalloproteinases and the subsequent activation of protease-activated receptor-1. J Immunol 2010, 185:615-623.
  • [56]Su X, Maguire-Zeiss KA, Giuliano R, Prifti L, Venkatesh K, Federoff HJ: Synuclein activates microglia in a model of Parkinson’s disease. Neurobiol Aging 2008, 29:1690-1701.
  • [57]Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, Wilson B, Zhang W, Zhou Y, Hong JS, Zhang J: Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. Faseb J 2005, 19:533-542.
  • [58]Jana M, Palencia CA, Pahan K: Fibrillar amyloid-beta peptides activate microglia via TLR2: implications for Alzheimer’s disease. J Immunol 2008, 181:7254-7262.
  • [59]Piers TM, Heales SJ, Pocock JM: Positive allosteric modulation of metabotropic glutamate receptor 5 down-regulates fibrinogen-activated microglia providing neuronal protection. Neurosci Lett 2011, 505:140-145.
  • [60]Lee DY, Oh YJ, Jin BK: Thrombin-activated microglia contribute to death of dopaminergic neurons in rat mesencephalic cultures: dual roles of mitogen-activated protein kinase signaling pathways. Glia 2005, 51:98-110.
  • [61]Siao CJ, Tsirka SE: Tissue plasminogen activator mediates microglial activation via its finger domain through annexin II. J Neurosci 2002, 22:3352-3358.
  • [62]Milner R, Crocker SJ, Hung S, Wang X, Frausto RF, del Zoppo GJ: Fibronectin- and vitronectin-induced microglial activation and matrix metalloproteinase-9 expression is mediated by integrins alpha5beta1 and alphavbeta5. J Immunol 2007, 178:8158-8167.
  • [63]Kim YS, Kim SS, Cho JJ, Choi DH, Hwang O, Shin DH, Chun HS, Beal MF, Joh TH: Matrix metalloproteinase-3: a novel signaling proteinase from apoptotic neuronal cells that activates microglia. J Neurosci 2005, 25:3701-3711.
  • [64]del Zoppo GJ, Milner R, Mabuchi T, Hung S, Wang X, Berg GI, Koziol JA: Microglial activation and matrix protease generation during focal cerebral ischemia. Stroke 2007, 38:646-651.
  • [65]Matsui T, Motoki Y, Inomoto T, Miura D, Kato Y, Suenaga H, Hino K, Nojima J: Temperature-Related Effects of Adenosine Triphosphate-Activated Microglia on Pro-Inflammatory Factors. Neurocrit Care 2011.
  • [66]Yasuda Y, Shimoda T, Uno K, Tateishi N, Furuya S, Yagi K, Suzuki K, Fujita S: The effects of MPTP on the activation of microglia/astrocytes and cytokine/chemokine levels in different mice strains. J Neuroimmunol 2008, 204:43-51.
  • [67]Gao HM, Hong JS, Zhang W, Liu B: Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 2002, 22:782-790.
  • [68]Wu XF, Block ML, Zhang W, Qin L, Wilson B, Zhang WQ, Veronesi B, Hong JS: The role of microglia in paraquat-induced dopaminergic neurotoxicity. Antioxid Redox Signal 2005, 7:654-661.
  • [69]McClain JA, Morris SA, Deeny MA, Marshall SA, Hayes DM, Kiser ZM, Nixon K: Adolescent binge alcohol exposure induces long-lasting partial activation of microglia. Brain Behav Immun 2011, 25(Suppl 1):S120-S128.
  • [70]Kuhn DM, Francescutti-Verbeem DM, Thomas DM: Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage. Ann N Y Acad Sci 2006, 1074:31-41.
  • [71]Lu DY, Tang CH, Chen YH, Wei IH: Berberine suppresses neuroinflammatory responses through AMP-activated protein kinase activation in BV-2 microglia. J Cell Biochem 2010, 110:697-705.
  • [72]Jung HW, Oh TW, Jung JK, Lee JH, Shin GJ, Park YK: Inhibitory Effects of the Methylene Chloride Fraction of JP05 on the Production of Inflammatory Mediators in LPS-activated BV2 Microglia. Inflammation 2010, 35:332-341.
  • [73]Meng XL, Yang JY, Chen GL, Zhang LJ, Wang LH, Li J, Wang JM, Wu CF: RV09, a novel resveratrol analogue, inhibits NO and TNF-alpha production by LPS-activated microglia. Int Immunopharmacol 2008, 8:1074-1082.
  • [74]Xu Y, Xue Y, Wang Y, Feng D, Lin S, Xu L: Multiple-modulation effects of Oridonin on the production of proinflammatory cytokines and neurotrophic factors in LPS-activated microglia. Int Immunopharmacol 2009, 9:360-365.
  • [75]Iribarren P, Chen K, Hu J, Zhang X, Gong W, Wang JM: IL-4 inhibits the expression of mouse formyl peptide receptor 2, a receptor for amyloid beta1-42, in TNF-alpha-activated microglia. J Immunol 2005, 175:6100-6106.
  • [76]Krady JK, Lin HW, Liberto CM, Basu A, Kremlev SG, Levison SW: Ciliary neurotrophic factor and interleukin-6 differentially activate microglia. J Neurosci Res 2008, 86:1538-1547.
  • [77]Tamakawa N, Saio M, Suwa T, Ohe N, Yoshimura S, Iwama T, Shinoda J, Sakai N, Takami T: Interleukin-2 activated microglia engulf tumor infiltrating T cells in the central nervous system. Int J Mol Med 2004, 13:497-503.
  • [78]Natarajan C, Sriram S, Muthian G, Bright JJ: Signaling through JAK2-STAT5 pathway is essential for IL-3-induced activation of microglia. Glia 2004, 45:188-196.
  • [79]Rozenfeld C, Martinez R, Seabra S, Sant’anna C, Goncalves JG, Bozza M, Moura-Neto V, De Souza W: Toxoplasma gondii prevents neuron degeneration by interferon-gamma-activated microglia in a mechanism involving inhibition of inducible nitric oxide synthase and transforming growth factor-beta1 production by infected microglia. Am J Pathol 2005, 167:1021-1031.
  • [80]Hall GL, Girdlestone J, Compston DA, Wing MG: Recall antigen presentation by gamma-interferon-activated microglia results in T cell activation and propagation of the immune response. J Neuroimmunol 1999, 98:105-111.
  • [81]Kim KS, Park JY, Jou I, Park SM: Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia. J Leukoc Biol 2009, 86:349-359.
  • [82]Min KJ, Yang MS, Kim SU, Jou I, Joe EH: Astrocytes induce hemeoxygenase-1 expression in microglia: a feasible mechanism for preventing excessive brain inflammation. J Neurosci 2006, 26:1880-1887.
  • [83]Zheng H, Zhu W, Zhao H, Wang X, Wang W, Li Z: Kainic acid-activated microglia mediate increased excitability of rat hippocampal neurons in vitro and in vivo: crucial role of interleukin-1beta. Neuroimmunomodulation 2010, 17:31-38.
  • [84]Zhu W, Zheng H, Shao X, Wang W, Yao Q, Li Z: Excitotoxicity of TNFalpha derived from KA activated microglia on hippocampal neurons in vitro and in vivo. J Neurochem 2010, 114:386-396.
  • [85]Aloisi F: Immune function of microglia. Glia 2001, 36:165-179.
  • [86]Neumann J, Sauerzweig S, Ronicke R, Gunzer F, Dinkel K, Ullrich O, Gunzer M, Reymann KG: Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: a new mechanism of CNS immune privilege. J Neurosci 2008, 28:5965-5975.
  • [87]Lee CY, Landreth GE: The role of microglia in amyloid clearance from the AD brain. J Neural Transm 2010, 117:949-960.
  • [88]Teismann P, Schulz JB: Cellular pathology of Parkinson’s disease: astrocytes, microglia and inflammation. Cell Tissue Res 2004, 318:149-161.
  • [89]Hill KE, Zollinger LV, Watt HE, Carlson NG, Rose JW: Inducible nitric oxide synthase in chronic active multiple sclerosis plaques: distribution, cellular expression and association with myelin damage. J Neuroimmunol 2004, 151:171-179.
  • [90]Mandrekar-Colucci S, Landreth GE: Microglia and inflammation in Alzheimer’s disease. CNS Neurol Disord Drug Targets 2010, 9:156-167.
  • [91]Kreutzberg GW: Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996, 19:312-318.
  • [92]Schwartz M, Butovsky O, Bruck W, Hanisch UK: Microglial phenotype: is the commitment reversible? Trends Neurosci 2006, 29:68-74.
  • [93]Hanisch UK: Microglia as a source and target of cytokines. Glia 2002, 40:140-155.
  • [94]Biber K, Neumann H, Inoue K, Boddeke HW: Neuronal ‘On’ and ‘Off’ signals control microglia. Trends Neurosci 2007, 30:596-602.
  • [95]Polazzi E, Contestabile A: Reciprocal interactions between microglia and neurons: from survival to neuropathology. Rev Neurosci 2002, 13:221-242.
  • [96]Zhou Y, Wang Y, Kovacs M, Jin J, Zhang J: Microglial activation induced by neurodegeneration: a proteomic analysis. Mol Cell Proteomics 2005, 4:1471-1479.
  • [97]Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM, Blom B, Homola ME, Streit WJ, Brown MH, et al.: Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 2000, 290:1768-1771.
  • [98]Chitnis T, Imitola J, Wang Y, Elyaman W, Chawla P, Sharuk M, Raddassi K, Bronson RT, Khoury SJ: Elevated neuronal expression of CD200 protects Wlds mice from inflammation-mediated neurodegeneration. Am J Pathol 2007, 170:1695-1712.
  • [99]Neumann H: Control of glial immune function by neurons. Glia 2001, 36:191-199.
  • [100]Wei R, Jonakait GM: Neurotrophins and the anti-inflammatory agents interleukin-4 (IL-4), IL-10, IL-11 and transforming growth factor-beta1 (TGF-beta1) down-regulate T cell costimulatory molecules B7 and CD40 on cultured rat microglia. J Neuroimmunol 1999, 95:8-18.
  • [101]Fukui K, Urano S, Koike T: Releasing factors from mature neurons modulate microglial survival via purinergic receptor activation. Neurosci Lett 2009, 456:64-68.
  • [102]Gehrmann J, Banati RB: Microglial turnover in the injured CNS: activated microglia undergo delayed DNA fragmentation following peripheral nerve injury. J Neuropathol Exp Neurol 1995, 54:680-688.
  • [103]Kuhlmann T, Bitsch A, Stadelmann C, Siebert H, Bruck W: Macrophages are eliminated from the injured peripheral nerve via local apoptosis and circulation to regional lymph nodes and the spleen. J Neurosci 2001, 21:3401-3408.
  • [104]Shuman SL, Bresnahan JC, Beattie MS: Apoptosis of microglia and oligodendrocytes after spinal cord contusion in rats. J Neurosci Res 1997, 50:798-808.
  • [105]White CA, McCombe PA, Pender MP: Microglia are more susceptible than macrophages to apoptosis in the central nervous system in experimental autoimmune encephalomyelitis through a mechanism not involving Fas (CD95). Int Immunol 1998, 10:935-941.
  • [106]Pais TF, Figueiredo C, Peixoto R, Braz MH, Chatterjee S: Necrotic neurons enhance microglial neurotoxicity through induction of glutaminase by a MyD88-dependent pathway. J Neuroinflammation 2008, 5:43. BioMed Central Full Text
  • [107]Eleuteri S, Polazzi E, Contestabile A: Neuroprotection of microglia conditioned media from apoptotic death induced by staurosporine and glutamate in cultures of rat cerebellar granule cells. Neurosci Lett 2008, 448:74-78.
  • [108]Moran LB, Graeber MB: The facial nerve axotomy model. Brain Res Brain Res Rev 2004, 44:154-178.
  • [109]Nakajima K, Tohyama Y, Maeda S, Kohsaka S, Kurihara T: Neuronal regulation by which microglia enhance the production of neurotrophic factors for GABAergic, catecholaminergic, and cholinergic neurons. Neurochem Int 2007, 50:807-820.
  • [110]Shih AY, Fernandes HB, Choi FY, Kozoriz MG, Liu Y, Li P, Cowan CM, Klegeris A: Policing the police: astrocytes modulate microglial activation. J Neurosci 2006, 26:3887-3888.
  • [111]Rohl C, Sievers J: Microglia is activated by astrocytes in trimethyltin intoxication. Toxicol Appl Pharmacol 2005, 204:36-45.
  • [112]Ovanesov MV, Ayhan Y, Wolbert C, Moldovan K, Sauder C, Pletnikov MV: Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection. J Neuroinflammation 2008, 5:50. BioMed Central Full Text
  • [113]von Bernhardi R, Eugenin J: Microglial reactivity to beta-amyloid is modulated by astrocytes and proinflammatory factors. Brain Res 2004, 1025:186-193.
  • [114]Ramirez G, Toro R, Dobeli H, von Bernhardi R: Protection of rat primary hippocampal cultures from A beta cytotoxicity by pro-inflammatory molecules is mediated by astrocytes. Neurobiol Dis 2005, 19:243-254.
  • [115]Aloisi F, Penna G, Cerase J, Menendez Iglesias B, Adorini L: IL-12 production by central nervous system microglia is inhibited by astrocytes. J Immunol 1997, 159:1604-1612.
  • [116]Pyo H, Yang MS, Jou I, Joe EH: Wortmannin enhances lipopolysaccharide-induced inducible nitric oxide synthase expression in microglia in the presence of astrocytes in rats. Neurosci Lett 2003, 346:141-144.
  • [117]Vincent VA, Van Dam AM, Persoons JH, Schotanus K, Steinbusch HW, Schoffelmeer AN, Berkenbosch F: Gradual inhibition of inducible nitric oxide synthase but not of interleukin-1 beta production in rat microglial cells of endotoxin-treated mixed glial cell cultures. Glia 1996, 17:94-102.
  • [118]Rouach N, Calvo CF, Glowinski J, Giaume C: Brain macrophages inhibit gap junctional communication and downregulate connexin 43 expression in cultured astrocytes. Eur J Neurosci 2002, 15:403-407.
  • [119]Rouach N, Calvo CF, Duquennoy H, Glowinski J, Giaume C: Hydrogen peroxide increases gap junctional communication and induces astrocyte toxicity: regulation by brain macrophages. Glia 2004, 45:28-38.
  • [120]Meme W, Calvo CF, Froger N, Ezan P, Amigou E, Koulakoff A, Giaume C: Proinflammatory cytokines released from microglia inhibit gap junctions in astrocytes: potentiation by beta-amyloid. Faseb J 2006, 20:494-496.
  • [121]Rohl C, Armbrust E, Kolbe K, Lucius R, Maser E, Venz S, Gulden M: Activated microglia modulate astroglial enzymes involved in oxidative and inflammatory stress and increase the resistance of astrocytes to oxidative stress in vitro. Glia 2008, 56:1114-1126.
  • [122]McCann MJ, O’Callaghan JP, Martin PM, Bertram T, Streit WJ: Differential activation of microglia and astrocytes following trimethyl tin-induced neurodegeneration. Neuroscience 1996, 72:273-281.
  • [123]Griffin WS: Inflammation and neurodegenerative diseases. Am J Clin Nutr 2006, 83:470S-474S.
  • [124]Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB: ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 2005, 8:752-758.
  • [125]Verderio C, Matteoli M: ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-gamma. J Immunol 2001, 166:6383-6391.
  • [126]Liu W, Tang Y, Feng J: Cross talk between activation of microglia and astrocytes in pathological conditions in the central nervous system. Life Sci 2011, 89:141-146.
  • [127]Giulian D, Baker TJ: Peptides released by ameboid microglia regulate astroglial proliferation. J Cell Biol 1985, 101:2411-2415.
  • [128]Tilleux S, Berger J, Hermans E: Induction of astrogliosis by activated microglia is associated with a down-regulation of metabotropic glutamate receptor 5. J Neuroimmunol 2007, 189:23-30.
  • [129]Savli H, Gulkac MD, Esen N: The effect of stimulated microglia conditioned media on BDNF gene expression of striatal astrocytes: quantification by real-time PCR. Int J Neurosci 2004, 114:1601-1612.
  • [130]Engelhardt B, Ransohoff RM: The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol 2005, 26:485-495.
  • [131]Re F, Belyanskaya SL, Riese RJ, Cipriani B, Fischer FR, Granucci F, Ricciardi-Castagnoli P, Brosnan C, Stern LJ, Strominger JL, Santambrogio L: Granulocyte-macrophage colony-stimulating factor induces an expression program in neonatal microglia that primes them for antigen presentation. J Immunol 2002, 169:2264-2273.
  • [132]Monsonego A, Imitola J, Zota V, Oida T, Weiner HL: Microglia-mediated nitric oxide cytotoxicity of T cells following amyloid beta-peptide presentation to Th1 cells. J Immunol 2003, 171:2216-2224.
  • [133]Shaked I, Porat Z, Gersner R, Kipnis J, Schwartz M: Early activation of microglia as antigen-presenting cells correlates with T cell-mediated protection and repair of the injured central nervous system. J Neuroimmunol 2004, 146:84-93.
  • [134]Goldman JE, Reynolds R: A reappraisal of ganglioside GD3 expression in the CNS. Glia 1996, 16:291-295.
  • [135]Kipnis J, Avidan H, Caspi RR, Schwartz M: Dual effect of CD4 + CD25+ regulatory T cells in neurodegeneration: a dialogue with microglia. Proc Natl Acad Sci U S A 2004, 101(Suppl 2):14663-14669.
  • [136]Beers DR, Henkel JS, Zhao W, Wang J, Appel SH: CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc Natl Acad Sci U S A 2008, 105:15558-15563.
  • [137]Ghasemlou N, Jeong SY, Lacroix S, David S: T cells contribute to lysophosphatidylcholine-induced macrophage activation and demyelination in the CNS. Glia 2007, 55:294-302.
  • [138]Levesque S, Wilson B, Gregoria V, Thorpe LB, Dallas S, Polikov VS, Hong JS, Block ML: Reactive microgliosis: extracellular micro-calpain and microglia-mediated dopaminergic neurotoxicity. Brain 2010, 133:808-821.
  • [139]Harry GJ, Kraft AD: Neuroinflammation and microglia: considerations and approaches for neurotoxicity assessment. Expert Opin Drug Metab Toxicol 2008, 4:1265-1277.
  • [140]Knoch ME, Hartnett KA, Hara H, Kandler K, Aizenman E: Microglia induce neurotoxicity via intraneuronal Zn(2+) release and a K(+) current surge. Glia 2008, 56:89-96.
  • [141]Qian L, Tan KS, Wei SJ, Wu HM, Xu Z, Wilson B, Lu RB, Hong JS, Flood PM: Microglia-mediated neurotoxicity is inhibited by morphine through an opioid receptor-independent reduction of NADPH oxidase activity. J Immunol 2007, 179:1198-1209.
  • [142]Diestel A, Troeller S, Billecke N, Sauer IM, Berger F, Schmitt KR: Mechanisms of hypothermia-induced cell protection mediated by microglial cells in vitro. Eur J Neurosci 2010, 31:779-787.
  • [143]Liang J, Takeuchi H, Jin S, Noda M, Li H, Doi Y, Kawanokuchi J, Sonobe Y, Mizuno T, Suzumura A: Glutamate induces neurotrophic factor production from microglia via protein kinase C pathway. Brain Res 2010, 1322:8-23.
  • [144]Walton NM, Sutter BM, Laywell ED, Levkoff LH, Kearns SM, Marshall GP, Scheffler B, Steindler DA: Microglia instruct subventricular zone neurogenesis. Glia 2006, 54:815-825.
  • [145]Thored P, Heldmann U, Gomes-Leal W, Gisler R, Darsalia V, Taneera J, Nygren JM, Jacobsen SE, Ekdahl CT, Kokaia Z, Lindvall O: Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia 2009, 57:835-849.
  • [146]McPherson CA, Kraft AD, Harry GJ: Injury-induced neurogenesis: consideration of resident microglia as supportive of neural progenitor cells. Neurotox Res 2011, 19:341-352.
  • [147]Sawada M, Sawada H, Nagatsu T: Effects of aging on neuroprotective and neurotoxic properties of microglia in neurodegenerative diseases. Neurodegener Dis 2008, 5:254-256.
  • [148]Conde JR, Streit WJ: Effect of aging on the microglial response to peripheral nerve injury. Neurobiol Aging 2006, 27:1451-1461.
  • [149]Luo XG, Ding JQ, Chen SD: Microglia in the aging brain: relevance to neurodegeneration. Mol Neurodegener 2010, 5:12. BioMed Central Full Text
  • [150]Streit WJ, Sammons NW, Kuhns AJ, Sparks DL: Dystrophic microglia in the aging human brain. Glia 2004, 45:208-212.
  • [151]Wasserman JK, Yang H, Schlichter LC: Glial responses, neuron death and lesion resolution after intracerebral hemorrhage in young vs. aged rats. Eur J Neurosci 2008, 28:1316-1328.
  • [152]Flanary BE, Sammons NW, Nguyen C, Walker D, Streit WJ: Evidence that aging and amyloid promote microglial cell senescence. Rejuvenation Res 2007, 10:61-74.
  • [153]Sugama S, Yang L, Cho BP, DeGiorgio LA, Lorenzl S, Albers DS, Beal MF, Volpe BT, Joh TH: Age-related microglial activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration in C57BL/6 mice. Brain Res 2003, 964:288-294.
  • [154]Sandhir R, Onyszchuk G, Berman NE: Exacerbated glial response in the aged mouse hippocampus following controlled cortical impact injury. Exp Neurol 2008, 213:372-380.
  • [155]Kyrkanides S, O’Banion MK, Whiteley PE, Daeschner JC, Olschowka JA: Enhanced glial activation and expression of specific CNS inflammation-related molecules in aged versus young rats following cortical stab injury. J Neuroimmunol 2001, 119:269-277.
  • [156]Kim KY, Ju WK, Neufeld AH: Neuronal susceptibility to damage: comparison of the retinas of young, old and old/caloric restricted rats before and after transient ischemia. Neurobiol Aging 2004, 25:491-500.
  • [157]Lu W, Bhasin M, Tsirka SE: Involvement of tissue plasminogen activator in onset and effector phases of experimental allergic encephalomyelitis. J Neurosci 2002, 22:10781-10789.
  • [158]Bhasin M, Wu M, Tsirka SE: Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis. BMC Immunol 2007, 8:10. BioMed Central Full Text
  • [159]El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD: Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 2007, 13:432-438.
  • [160]Gordon S: Alternative activation of macrophages. Nat Rev Immunol 2003, 3:23-35.
  • [161]Gordon S, Taylor PR: Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005, 5:953-964.
  • [162]Wynn TA, Thompson RW, Cheever AW, Mentink-Kane MM: Immunopathogenesis of schistosomiasis. Immunol Rev 2004, 201:156-167.
  • [163]Herber DL, Mercer M, Roth LM, Symmonds K, Maloney J, Wilson N, Freeman MJ, Morgan D, Gordon MN: Microglial activation is required for Abeta clearance after intracranial injection of lipopolysaccharide in APP transgenic mice. J Neuroimmune Pharmacol 2007, 2:222-231.
  • [164]Akiyama H: Inflammatory response in Alzheimer’s disease. Tohoku J Exp Med 1994, 174:295-303.
  • [165]Ciaramella A, Bizzoni F, Salani F, Vanni D, Spalletta G, Sanarico N, Vendetti S, Caltagirone C, Bossu P: Increased pro-inflammatory response by dendritic cells from patients with Alzheimer’s disease. J Alzheimers Dis 2010, 19:559-572.
  • [166]Rogers J: The inflammatory response in Alzheimer’s disease. J Periodontol 2008, 79:1535-1543.
  • [167]Colton CA, Mott RT, Sharpe H, Xu Q, Van Nostrand WE, Vitek MP: Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. J Neuroinflammation 2006, 3:27. BioMed Central Full Text
  • [168]Sawada H, Suzuki H, Nagatsu T, Sawada M: Neuroprotective and neurotoxic phenotypes of activated microglia in neonatal mice with respective MPTP- and ethanol-induced brain injury. Neurodegener Dis 2010, 7:64-67.
  • [169]Lai AY, Todd KG: Differential regulation of trophic and proinflammatory microglial effectors is dependent on severity of neuronal injury. Glia 2008, 56:259-270.
  • [170]Hald A, Nedergaard S, Hansen RR, Ding M, Heegaard AM: Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain. Eur J Pain 2009, 13:138-145.
  • [171]Carson MJ, Reilly CR, Sutcliffe JG, Lo D: Mature microglia resemble immature antigen-presenting cells. Glia 1998, 22:72-85.
  • [172]Ekdahl CT, Kokaia Z, Lindvall O: Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 2009, 158:1021-1029.
  • [173]Aarum J, Sandberg K, Haeberlein SL, Persson MA: Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci U S A 2003, 100:15983-15988.
  • [174]Luo X, Ge C, Ren Y, Zhou J, Li X, Yan R, Zhang C: BV2 enhanced the neurotrophic functions of mesenchymal stem cells after being stimulated with injured PC12. Neuroimmunomodulation 2009, 16:28-34.
  • [175]Luo XG, Wang H, Zhou J, Yan R, Wu Z, Zhang CD, Wang QS: Beneficial effects of BV2 cell on proliferation and neuron-differentiating of mesenchymal stem cells in the circumstance of injured PC12 cell supernatant. Neurosci Bull 2006, 22:221-226.
  • [176]Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O: Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A 2003, 100:13632-13637.
  • [177]Monje ML, Toda H, Palmer TD: Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003, 302:1760-1765.
  • [178]Yang F, Liu ZR, Chen J, Zhang SJ, Quan QY, Huang YG, Jiang W: Roles of astrocytes and microglia in seizure-induced aberrant neurogenesis in the hippocampus of adult rats. J Neurosci Res 2010, 88:519-529.
  • [179]Monje ML, Mizumatsu S, Fike JR, Palmer TD: Irradiation induces neural precursor-cell dysfunction. Nat Med 2002, 8:955-962.
  • [180]Battista D, Ferrari CC, Gage FH, Pitossi FJ: Neurogenic niche modulation by activated microglia: transforming growth factor beta increases neurogenesis in the adult dentate gyrus. Eur J Neurosci 2006, 23:83-93.
  • [181]Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, Martino G, Schwartz M: Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci 2006, 31:149-160.
  • [182]Aberg MA, Aberg ND, Palmer TD, Alborn AM, Carlsson-Skwirut C, Bang P, Rosengren LE, Olsson T, Gage FH, Eriksson PS: IGF-I has a direct proliferative effect in adult hippocampal progenitor cells. Mol Cell Neurosci 2003, 24:23-40.
  • [183]Choi YS, Cho HY, Hoyt KR, Naegele JR, Obrietan K: IGF-1 receptor-mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus. Glia 2008, 56:791-800.
  • [184]Butovsky O, Hauben E, Schwartz M: Morphological aspects of spinal cord autoimmune neuroprotection: colocalization of T cells with B7–2 (CD86) and prevention of cyst formation. Faseb J 2001, 15:1065-1067.
  • [185]Buckwalter MS, Yamane M, Coleman BS, Ormerod BK, Chin JT, Palmer T, Wyss-Coray T: Chronically increased transforming growth factor-beta1 strongly inhibits hippocampal neurogenesis in aged mice. Am J Pathol 2006, 169:154-164.
  • [186]Ogita K, Nishiyama N, Sugiyama C, Higuchi K, Yoneyama M, Yoneda Y: Regeneration of granule neurons after lesioning of hippocampal dentate gyrus: evaluation using adult mice treated with trimethyltin chloride as a model. J Neurosci Res 2005, 82:609-621.
  • [187]Harry GJ, McPherson CA, Wine RN, Atkinson K, Lefebvre d’Hellencourt C: Trimethyltin-induced neurogenesis in the murine hippocampus. Neurotox Res 2004, 5:623-627.
  • [188]Kuhn HG, Dickinson-Anson H, Gage FH: Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 1996, 16:2027-2033.
  • [189]Knoth R, Singec I, Ditter M, Pantazis G, Capetian P, Meyer RP, Horvat V, Volk B, Kempermann G: Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS One 2010, 5:e8809.
  • [190]Zhu C, Qiu L, Wang X, Xu F, Nilsson M, Cooper-Kuhn C, Kuhn HG, Blomgren K: Age-dependent regenerative responses in the striatum and cortex after hypoxia-ischemia. J Cereb Blood Flow Metab 2009, 29:342-354.
  • [191]Ransohoff RM, Kivisakk P, Kidd G: Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 2003, 3:569-581.
  • [192]Ziv Y, Finkelstein A, Geffen Y, Kipnis J, Smirnov I, Shpilman S, Vertkin I, Kimron M, Lange A, Hecht T, et al.: A novel immune-based therapy for stroke induces neuroprotection and supports neurogenesis. Stroke 2007, 38:774-782.
  • [193]Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, Cohen H, Kipnis J, Schwartz M: Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 2006, 9:268-275.
  文献评价指标  
  下载次数:9次 浏览次数:2次