CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on astrocytes

被引:42
作者
Catalano, Myriam [1 ,2 ]
Lauro, Clotilde [1 ]
Cipriani, Raffaela [1 ]
Chece, Giuseppina [1 ]
Ponzetta, Andrea [1 ]
Di Angelantonio, Silvia [1 ,3 ]
Ragozzino, Davide [1 ,2 ]
Limatola, Cristina [1 ,2 ]
机构
[1] Univ Roma La Sapienza, Dept Physiol & Pharmacol, Fdn Cenci Bolognetti, I-00185 Rome, Italy
[2] IRCCS Neuromed, I-86077 Pozzilli, Italy
[3] Ist Italiano Tecnol, Ctr Life Nano Sci Sapienza, Rome, Italy
关键词
CX3CL1; Neuroprotection; GLT-1; Astrocytes; Microglia; A1R; SENSITIVE EAAT2 EXPRESSION; FOCAL CEREBRAL-ISCHEMIA; GLUTAMATE UPTAKE; FRACTALKINE-RECEPTOR; CULTURED ASTROCYTES; HIPPOCAMPAL-NEURONS; DOWN-REGULATION; ADENOSINE; NEUROPROTECTION; TRANSPORTERS;
D O I
10.1016/j.jneuroim.2013.07.020
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this paper we show for the first time that: i) astrocytes are required for the neuroprotective activity of CX3CL1 against excitotoxicity; ii) inhibition of the glutamate transporter 1 (GLT-1) prejudices CX3CL1-mediated neuroprotection; iii) CX3CL1 increases GLT-1 activity on astrocytes. The modulation of GLT-1 activity induced by CX3CL1 on astrocytes requires the presence and the activity of A1 adenosine receptor (A(1)R), being blocked by the specific antagonist DPCPX and absent in A(1)R(-/-) astrocytes. These data introduce the astrocytes as active players in CX3CL1-mediated signaling between microglia and neurons, identifying GLT-1 as a key mediator of the neuroprotective activity of CX3CL1. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:75 / 82
页数:8
相关论文
共 52 条
[11]   Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease [J].
Fuhrmann, Martin ;
Bittner, Tobias ;
Jung, Christian K. E. ;
Burgold, Steffen ;
Page, Richard M. ;
Mitteregger, Gerda ;
Haass, Christian ;
LaFerla, Frank M. ;
Kretzschmar, Hans ;
Herms, Jochen .
NATURE NEUROSCIENCE, 2010, 13 (04) :411-413
[12]   The tripartite synapse: roles for gliotransmission in health and disease [J].
Halassa, Michael M. ;
Fellin, Tommaso ;
Haydon, Philip G. .
TRENDS IN MOLECULAR MEDICINE, 2007, 13 (02) :54-63
[13]   Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia [J].
Harrison, JK ;
Jiang, Y ;
Chen, SZ ;
Xia, YY ;
Maciejewski, D ;
McNamara, RK ;
Streit, WJ ;
Salafranca, MN ;
Adhikari, S ;
Thompson, DA ;
Botti, P ;
Bacon, KB ;
Feng, LL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (18) :10896-10901
[14]   Down-regulation of the macrophage lineage through interaction with OX2 (CD200) [J].
Hoek, RM ;
Ruuls, SR ;
Murphy, CA ;
Wright, GJ ;
Goddard, R ;
Zurawski, SM ;
Blom, B ;
Homola, ME ;
Streit, WJ ;
Brown, MH ;
Barclay, AN ;
Sedgwick, JD .
SCIENCE, 2000, 290 (5497) :1768-1771
[15]   The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system [J].
Huang, Deren ;
Shi, Fu-Dong ;
Jung, Steffen ;
Pien, Gary C. ;
Wang, Jintang ;
Salazar-Mather, Thais P. ;
He, Toby T. ;
Weaver, Jennifer T. ;
Ljunggren, Hans-Gustaf ;
Biron, Christine A. ;
Littman, Dan R. ;
Ransohoff, Richard M. .
FASEB JOURNAL, 2006, 20 (07) :896-905
[16]   Different expression role among glutamate transporters in rat retinal glial cells under various culture conditions [J].
Imasawa, M ;
Kashiwagi, K ;
Iizuka, Y ;
Tanaka, M ;
Tsukahara, S .
MOLECULAR BRAIN RESEARCH, 2005, 142 (01) :1-8
[17]   Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor [J].
Johansson, B ;
Halldner, L ;
Dunwiddie, TV ;
Masino, SA ;
Poelchen, W ;
Giménez-Llort, L ;
Escorihuela, RM ;
Fernández-Teruel, A ;
Wiesenfeld-Hallin, Z ;
Xu, XJ ;
Hårdemark, A ;
Betsholtz, C ;
Herlenius, E ;
Fredholm, BB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) :9407-9412
[18]   Analysis of fractalkine receptor CX3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion [J].
Jung, S ;
Aliberti, J ;
Graemmel, P ;
Sunshine, MJ ;
Kreutzberg, GW ;
Sher, A ;
Littman, DR .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (11) :4106-4114
[19]   Role of Excitatory Amino Acid Transporter-2 (EAAT2) and Glutamate in Neurodegeneration: Opportunities for Developing Novel Therapeutics [J].
Kim, Keetae ;
Lee, Seok-Geun ;
Kegelman, Timothy P. ;
Su, Zhao-Zhong ;
Das, Swadesh K. ;
Dash, Rupesh ;
Dasgupta, Santanu ;
Barral, Paola M. ;
Hedvat, Michael ;
Diaz, Paul ;
Reed, John C. ;
Stebbins, John L. ;
Pellecchia, Maurizio ;
Sarkar, Devanand ;
Fisher, Paul B. .
JOURNAL OF CELLULAR PHYSIOLOGY, 2011, 226 (10) :2484-2493
[20]   Adenosine in the central nervous system: release mechanisms and extracellular concentrations [J].
Latini, S ;
Pedata, F .
JOURNAL OF NEUROCHEMISTRY, 2001, 79 (03) :463-484