CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer's disease model

Journal of Clinical Investigation

Volumn 125, Issue 1, 2015, Pages 365-378

  Krauthausen, Marius ^a   Kummer, Markus P ^a   Zimmermann, Julian ^a   Reyes Irisarri, Elisabet ^a   Terwel, Dick ^a   Bulic, Bruno ^b   Heneka, Michael T ^a   Müller, Marcus ^a  

^a UNIVERSITY HOSPITAL BONN   (Germany)

^b HUMBOLDT UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; CHEMOKINE RECEPTOR CXCR3; PRESENILIN 1; TUMOR NECROSIS FACTOR ALPHA; CXCL10 PROTEIN, MOUSE; CXCL9 CHEMOKINE; CXCL9 PROTEIN, MOUSE; CXCR3 PROTEIN, MOUSE; GAMMA INTERFERON INDUCIBLE PROTEIN 10;

ALZHEIMER DISEASE; AMYLOID PLAQUE; ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; BEHAVIOR; BEHAVIOR DISORDER; BRAIN TISSUE; CELL ACTIVATION; CELL PHAGOCYTOSIS; COGNITIVE DEFECT; CONTROLLED STUDY; CYTOKINE RELEASE; HIPPOCAMPUS; IN VITRO STUDY; IN VIVO STUDY; MALE; MICROGLIA; MOUSE; NERVE CELL STIMULATION; NONHUMAN; PATHOLOGY; PLAQUE FORMING CELL; SIGNAL TRANSDUCTION; SPATIAL LEARNING; SPATIAL MEMORY; TRANSGENIC MOUSE; ANIMAL; C57BL MOUSE; CELL CULTURE; FEMALE; GENETICS; KNOCKOUT MOUSE; MAZE TEST; METABOLISM; PHAGOCYTOSIS; PHYSIOLOGY; SECRETION (PROCESS); TRANSCRIPTION INITIATION;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; ASTROCYTES; CELLS, CULTURED; CHEMOKINE CXCL10; CHEMOKINE CXCL9; FEMALE; MALE; MAZE LEARNING; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROGLIA; PHAGOCYTOSIS; PLAQUE, AMYLOID; RECEPTORS, CXCR3; SIGNAL TRANSDUCTION; TRANSCRIPTIONAL ACTIVATION; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84920488634     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI66771     Document Type: Article

References (94)

1. Katzman R, Saitoh T. Advances in Alzheimer's disease. FASEB J. 1991;5(3):278-286.
2. Mattson MP. Pathways towards and away from Alzheimer's disease. Nature. 2004;430(7000):631-639.
3. Heneka MT, O'Banion MK, Terwel D, Kummer MP. Neuroinflammatory processes in Alzheimer's disease. J Neural Transm. 2010;117(8):919-947.
4. Parpura V, et al. Glial cells in (patho)physiology. J Neurochem. 2012;121(1):4-27.
5. Perry VH, Gordon S. Macrophages and microg-lia in the nervous system. Trends Neurosci. 1988;11(6):273-277.
6. Lawson LJ, Perry VH, Gordon S. Turnover of resident microglia in the normal adult mouse brain. Neuroscience. 1992;48(2):405-415.
7. Koenigsknecht-Talboo J, Landreth GE. Microglial phagocytosis induced by fibrillar β-amyloid and IgGs are differentially regulated by proinflamma-tory cytokines. J Neurosci. 2005;25(36):8240-8249.
8. Shie F-S, Breyer RM, Montine TJ. Microglia lacking E Prostanoid Receptor subtype 2 have enhanced Aβ phagocytosis yet lack Aβ-activated neurotoxic-ity. Am J Pathol. 2005;166(4):1163-1172.
9. Yamamoto M, et al. Overexpression of mono-cyte chemotactic protein-1/CCL2 in β-amyloid precursor protein transgenic mice show accelerated diffuse β-amyloid deposition. Am J Pathol. 2005;166(5):1475-1485.
10. Town T, et al. Blocking TGF-[beta]-Smad2/3 innate immune signaling mitigates Alzheimerlike pathology. Nat Med. 2008;14(6):681-687.
11. Krause DL, Müller N. Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer's disease. Int J Alzheimer Dis. 2010;2010:732806.
12. Reed-Geaghan EG, Reed QW, Cramer PE, Landreth GE. Deletion of CD14 attenuates Alzheimer's disease pathology by influencing the brain's inflammatory milieu. J Neurosci. 2010;30(46):15369-15373.
13. Heneka MT, et al. NLRP3 is activated in Alzheimer/'s disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493(7434):674-678.
14. Wyss-Coray T, Mucke L. Inflammation in neuro-degenerative disease - a double-edged sword. Neuron. 2002;35(3):419-432.
15. Paresce D, Ghosh R, Maxfield F. Microglial cells internalize aggregates of the Alzheimer's disease Amyloid β-protein via a scavenger receptor. Neuron. 1996;17(3):553-565.
16. Weldon DT, et al. Fibrillar β-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo. J Neurosci. 1998;18(6):2161-2173.
17. Koenigsknecht J, Landreth G. Microglial phagocytosis of fibrillar β-amyloid through a β1 integrin-dependent mechanism. J Neurosci. 2004;24(44):9838-9846.
18. Charo IF, Ransohoff RM. The many roles of che-mokines and chemokine receptors in inflammation. N Engl J Med. 2006;354(6):610-621.
19. Müller M, Carter S, Hofer MJ, Campbell IL. Review: The chemokine receptor CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 in neu-roimmunity - a tale of conflict and conundrum. Neuropathol Appl Neurobiol. 2010;36(5):368-387.
20. Loetscher M, et al. Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J Exp Med. 1996;184(3):963-969.
21. Weng Y, et al. Binding and functional properties of recombinant and endogenous CXCR3 chemokine receptors. J Biol Chem. 1998;273(29):18288-18291.
22. Sallusto F, Lanzavecchia A. Understanding dendritic cell and T-lymphocyte traffic through the analysis of chemokine receptor expression. Immunol Rev. 2000;177:134-140.
23. Biber K, et al. Functional expression of CXCR3 in cultured mouse and human astrocytes and microglia. Neuroscience. 2002;112(3):487-497.
24. Flynn G. Regulation of chemokine receptor expression in human microglia and astrocytes. J Neuroimmunol. 2003;136(1-2):84-93.
25. Rappert A, et al. CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion. J Neurosci. 2004;24(39):8500-8509.
26. De Jong EK, et al. Expression of CXCL4 in microglia in vitro and in vivo and its possible signaling through CXCR3. J Neurochem. 2008;105(5):1726-1736.
27. Xia MQ, Bacskai BJ, Knowles RB, Qin SX, Hyman BT. Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role in Alzheimer's disease. J Neuroimmunol. 2000;108(1-2):227-235.
28. Nelson TE, Gruol DL. The chemokine CXCL10 modulates excitatory activity and intracellular calcium signaling in cultured hippocampal neurons. J Neuroimmunol. 2004;156(1-2):74-87.
29. Zhang B, Patel J, Croyle M, Diamond MS, Klein RS. TNF-alpha-dependent regulation of CXCR3 expression modulates neuronal survival during West Nile virus encephalitis. J Neuroimmunol. 2010;224(1-2):28-38.
30. Loetscher M, Loetscher P, Brass N, Meese E, Moser B. Lymphocyte-specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization. Eur J Immunol. 1998;28(11):3696-3705.
31. Luster AD, Unkeless JC, Ravetch JV. y-Interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985;315(6021):672-676.
32. Cole KE, et al. Interferon-inducible T cell a che-moattractant (I-TAC): a novel non-ELR CXC che-mokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med. 1998;187(12):2009-2021.
33. Carter SL, Müller M, Manders PM, Campbell IL. Induction of the genes for Cxcl9 and Cxcl10 is dependent on IFN-y but shows differential cellular expression in experimental autoimmune encephalomyelitis and by astrocytes and microglia in vitro. Glia. 2007;55(16):1728-1739.
34. Zhang B, Patel J, Croyle M, Diamond MS, Klein RS. TNF-alpha-dependent regulation of CXCR3 expression modulates neuronal survival during West Nile virus encephalitis. J Neuroimmunol. 2010;2 24(1-2):28-38.
35. Choi K, Ni L, Jonakait GM. Fas ligation and tumor necrosis factor alpha activation of murine astrocytes promote heat shock factor-1 activation and heat shock protein expression leading to che-mokine induction and cell survival. J Neurochem. 2011;116(3):438-448.
36. Lee YK, et al. CCR5 deficiency induces astrocyte activation, Abeta deposit and impaired memory function. Neurobiol Learn Mem. 2009; 92(3): 356-363.
37. El Khoury J, et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med. 2007;13(4):432-438.
38. Kiyota T, et al. CCL2 accelerates microglia-mediated Aß oligomer formation and progression of neurocognitive dysfunction. PLoS One. 2009;4(7):e6197
39. Semple BD, Frugier T, Morganti-Kossmann MC. CCL2 modulates cytokine production in cultured mouse astrocytes. J Neuroinflammation. 2010;7:67.
40. Fuhrmann M, et al. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nat Neurosci. 2010;13(4):411-413.
41. Lee S, et al. CX3CR1 deficiency alters microglial activation and reduces ß-amyloid deposition in two Alzheimer's disease mouse models. Am J Pathol. 2010;177(5):2549-2562.
42. Liu Z, Condello C, Schain A, Harb R, Grut-zendler J. CX3CR1 in microglia regulates brain amyloid deposition through selective proto-fibrillar amyloid-ß phagocytosis. J Neurosci. 2010;30(50):17091-17101.
43. Nash KR, et al. Fractalkine overexpression suppresses tau pathology in a mouse model of tauop-athy. Neurobiol Aging. 2013;34(6):1540-1548.
44. Galimberti D, Schoonenboom N, Scarpini E, Scheltens P. Chemokines in serum and cerebrospinal fluid of Alzheimer's disease patients. Ann Neurol. 2003;53(4):547-548.
45. Galimberti D, et al. Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Arch Neurol. 2006;63(4):538-543.
46. Duan R-S, et al. Decreased fractalkine and increased IP-10 expression in aged brain of APP(swe) transgenic mice. Neurochem Res. 2008;33(6):1085-1089.
47. Jankowsky JL, et al. Mutant presenilins specifically elevate the levels of the 42 residue ß-amyloid peptide in vivo: evidence for augmentation of a 42-specificy secretase. Hum Mol Genet. 2004;13(2):159-170.
48. Garcia-Alloza M, et al. Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis. 2006;24(3):516-524.
49. Ruan L, Kang Z, Pei G, Le Y. Amyloid deposition and inflammation in APPswe/PS1dE9 mouse model of Alzheimer's disease. Curr Alzheimer Res. 2009;6(6):531-540.
50. Hammerschmidt T, et al. Selective loss of noradrenaline exacerbates early cognitive dysfunction and synaptic deficits in APP/PS1 mice. Biol Psychiatry. 2013;73(5):454-463.
51. Jankowsky JL, et al. Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng. 2001;17(6):157-165.
52. Cho J, Nelson TE, Bajova H, Gruol DL. Chronic CXCL10 alters neuronal properties in rat hippocampal culture. J Neuroimmunol. 2 009;207(1-2): 92-100.
53. Sui Y, et al. CXCL10-induced cell death in neurons: role of calcium dysregulation. Eur J Neuro-sci. 2006;23(4):957-964.
54. Coughlan CM, et al. Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons. Neuroscience. 2000;97(3) 591-600.
55. Riemer C, et al. Accelerated prion replication in, but prolonged survival times of, prion-infected CXCR3-/-mice. J Virol. 2008;82(24):12464-12471.
56. Koistinaho M, et al. Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-ß peptides. Nat Med. 2004;10(7):719-726.
57. Farina C, Aloisi F, Meinl E. Astrocytes are active players in cerebral innate immunity. Trends Immunol. 2007;28(3):138-145.
58. Van Weering HRJ, et al. CXCL10/CXCR3 signaling in glia cells differentially affects NMDA-induced cell death in CA and DG neurons of the mouse hippocampus. Hippocampus. 2 011;21(2):2 2 0-2 3 2.
59. Amor S, Puentes F, Baker D, van der Valk P. Inflammation in neurodegenerative diseases. Immunology. 2010;129(2):154-169.
60. Ramos EM, et al. Tumor necrosis factor a and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease. Arch Neurol. 2006;63(8):1165-1169.
61. Tobinick E, Gross H, Weinberger A, Cohen H. TNF-α modulation for treatment of Alzheimer's disease: a 6-month pilot study. Med Gen Med. 2006;8(2):25.
62. Pardridge WM. Biologic TNFα-inhibitors that cross the human blood-brain barrier. Bioeng Bugs. 2010;1(4):231-234.
63. Frankola KA, Greig NH, Luo W, Tweedie D. Targeting TNF-α to elucidate and ameliorate neuroinflammation in neurodegenerative diseases. CNS Neurol Disord Drug Targets. 2011;10(3):391-403.
64. McAlpine FE, et al. Inhibition of soluble TNF signaling in a mouse model of Alzheimer's disease prevents pre-plaque amyloid-associated neuro-pathology. Neurobiol Dis. 2009;34(1):163-177.
65. Hofmann K, Tschopp J. The death domain motif found in Fas (Apo-1) and TNF receptor is present in proteins involved in apoptosis and axonal guidance. FEBS Lett. 1995;371(3):321-323.
66. Felderhoff-Mueser U, et al. Fas/CD95/APO-1 can function as a death receptor for neuronal cells in vitro and in vivo and is upregulated following cerebral hypoxic-ischemic injury to the developing rat brain. Brain Pathol. 2000;10(1):17-29.
67. Ethell DW, Buhler LA. Fas ligand-mediated apop-tosis in degenerative disorders of the brain. J Clin Immunol. 2003;23(6):439-446.
68. Su JH, et al. Fas and Fas ligand are associated with neuritic degeneration in the AD brain and participate in β-amyloid-induced neuronal death. Neurobiol Dis. 2003;12(3):182-193.
69. Shaftel SS, et al. Sustained hippocampal IL-1 β overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J Clin Invest. 2007;117(6):1595-1604.
70. Pinteaux E, Trotter P, Simi A. Cell-specific and concentration-dependent actions of interleu-kin-1 in acute brain inflammation. Cytokine. 2009;45(1):1-7.
71. Müller M, et al. CXCR3 signaling reduces the severity of experimental autoimmune encephalomyelitis by controlling the parenchy-mal distribution of effector and regulatory T cells in the central nervous system. J Immunol. 2007;179(5):2774-2786.
72. Miu J, et al. Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency. J Immunol. 2008;180(2):1217-1230.
73. Christensen JE, et al. Efficient T-cell surveillance of the CNS requires expression of the CXC chemokine receptor 3. J Neurosci. 2004;24(20):4849-4858.
74. Zhang W, Wang PJ, Sha HY, Ni J, Li MH, Gu GJ. Neural stem cell transplants improve cognitive function without altering amyloid pathology in an APP/PS1 double transgenic model of Alzheimer's disease. Mol Neurobiol. 2014;50(2):423-437.
75. Nagahara AH, et al. Early BDNF treatment ameliorates cell loss in the entorhinal cortex of APP trans-genic mice. J Neurosci. 2013;33(39):15596-15602.
76. Klegeris A, Walker DG, McGeer PL. Interaction of Alzheimer β-amyloid peptide with the human monocytic cell line THP-1 results in a protein kinase C-dependent secretion of tumor necrosis factor-alpha. Brain Res. 1997;747(1):114-121.
77. Gregersen R, Lambertsen K, Finsen B. Microglia and macrophages are the major source of tumor necrosis factor in permanent middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab. 2000;20(1):53-65.
78. Lue LF, et al. Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro. Glia. 2001;35(1):72-79.
79. Hanisch U-K. Microglia as a source and target of cytokines. Glia. 2002;40(2):140-155.
80. Ferber I, et al. Mice with a disrupted IFN-y gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol. 1996;156(1):5-7
81. Majumder S, et al. Regulation of human IP-10 gene expression in astrocytoma cells by inflammatory cytokines. J Neurosci Res. 1998;54(2):169-180.
82. Smit MJ, Lira SA, Leurs R. Chemokine Receptors as Drug Targets. Malden, Massachusetts, USA: John Wiley & Sons; 2010.
83. Krauthausen M, et al. Opposing roles for CXCR3 signaling in central nervous system versus ocular inflammation mediated by the astrocyte-targeted production of IL-12. Am J Pathol. 2011;179(5):2346-2359.
84. Hancock WW, et al. Requirement of the chemokine receptor CXCR3 for acute allograft rejection. J Exp Med. 2000;192(10):1515-1520.
85. Candore G, et al. Age-related inflammatory diseases: role of genetics and gender in the pathophysiology of Alzheimer's disease. Ann N Y Acad Sci. 2006;1089:472-486.
86. Casadesus G, et al. The estrogen myth: potential use of gonadotropin-releasing hormone agonists for the treatment of Alzheimer's disease. Drugs R D. 2006;7(3):187-193.
87. Müller M, Wacker K, Getts D, Ringelstein EB, Kiefer R. Further evidence for a crucial role of resident endoneurial macrophages in peripheral nerve disorders: Lessons from acrylamide-induced neuropathy. Glia. 2008;56(9):1005-1016.
88. Martin LJ, et al. Amyloid precursor protein in aged nonhuman primates. Proc Natl Acad Sci U S A. 1991;88(4):1461-1465.
89. Hanisch U-K, et al. The microglia-acti-vating potential of thrombin. J Biol Chem. 2004;279(50):51880-51887.
90. Teplow DB. Preparation of amyloid beta-protein for structural and functional studies. Meth Enzy-mol. 2006;413:20-33.
91. Fleisher-Berkovich S, et al. Distinct modulation of microglial amyloid ß phagocytosis and migration by neuropeptides (i). J Neuroinflammation. 2010;7:61.
92. Hayes ME, et al. Discovery of small molecule benzimidazole antagonists of the chemokine receptor CXCR3. Bioorg Medicinal Chem Lett. 2008;18(5):1573-1576.
93. Kummer MP, et al. Nitration of tyrosine 10 critically enhances amyloid ß aggregation and plaque formation. Neuron. 2011;71(5):833-844.
94. Jäger S, et al. a-secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C8 3 limits Aß generation. J Neuro-chem. 2009;111(6):1369-1382.