Neuronal Chemokines: Versatile Messengers In Central Nervous System Cell Interaction

Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS), chemokines are generally found under both physiological and pathological conditions. Whereas many reports describe chemokine expression in astrocytes and microglia and their role in the migration of leukocytes into the CNS, only few studies describe chemokine expression in neurons. Nevertheless, the expression of neuronal chemokines and the corresponding chemokine receptors in CNS cells under physiological and pathological conditions indicates that neuronal chemokines contribute to CNS cell interaction. In this study, we review recent studies describing neuronal chemokine expression and discuss potential roles of neuronal chemokines in neuron–astrocyte, neuron–microglia, and neuron–neuron interaction.

[1]  J. P. Schwartz,et al.  Treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium‐derived factor in vitro enhances expression of other neurotrophic factors as well as cytokines and chemokines , 2004, Journal of neuroscience research.

[2]  C. Achim,et al.  Haptoglobin polymorphism, iron metabolism and mortality in HIV infection , 1998 .

[3]  P. Murphy Chemokine receptors: structure, function and role in microbial pathogenesis. , 1996, Cytokine & growth factor reviews.

[4]  N. Copeland,et al.  The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  B. Brew,et al.  Expression of chemokines and their receptors in human and simian astrocytes: Evidence for a central role of TNFα and IFNγ in CXCR4 and CCR5 modulation , 2003 .

[6]  J. Vincent,et al.  Isolated human astrocytes are not susceptible to infection by M‐ and T‐tropic HIV‐1 strains despite functional expression of the chemokine receptors CCR5 and CXCR4 , 2001, Glia.

[7]  F. Eusebi,et al.  Modulation of the neurotransmitter release in rat cerebellar neurons by GRO beta. , 1998, Neuroreport.

[8]  B Carragher,et al.  Three-Dimensional Analysis of the Relationship Between Synaptic Pathology and Neuropil Threads in Alzheimer Disease , 1992, Journal of neuropathology and experimental neurology.

[9]  I. Bechmann,et al.  Involvement of Non‐Neuronal Cells in Entorhinal‐Hippocampal Reorganization Following Lesions , 2000, Annals of the New York Academy of Sciences.

[10]  C. Blobel,et al.  Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1). , 2001, The Journal of biological chemistry.

[11]  W. Rostène,et al.  Highly regionalized distribution of stromal cell‐derived factor‐1/CXCL12 in adult rat brain: constitutive expression in cholinergic, dopaminergic and vasopressinergic neurons , 2003, The European journal of neuroscience.

[12]  M. Dorf,et al.  Astrocytes express functional chemokine receptors , 2000, Journal of Neuroimmunology.

[13]  A. Suzumura,et al.  Production and neuroprotective functions of fractalkine in the central nervous system , 2003, Brain Research.

[14]  Stuart A. Lipton,et al.  Pathways to neuronal injury and apoptosis in HIV-associated dementia , 2001, Nature.

[15]  A. Sher,et al.  Analysis of Fractalkine Receptor CX3CR1 Function by Targeted Deletion and Green Fluorescent Protein Reporter Gene Insertion , 2000, Molecular and Cellular Biology.

[16]  W. Streit,et al.  TGF-β1 upregulates CX3CR1 expression and inhibits fractalkine-stimulated signaling in rat microglia , 2002, Journal of Neuroimmunology.

[17]  M. Dorf,et al.  RANTES stimulates inflammatory cascades and receptor modulation in murine astrocytes , 2002, Glia.

[18]  Guo-Yuan Yang,et al.  Reduction of Inflammatory Response in the Mouse Brain With Adenoviral-Mediated Transforming Growth Factor-&bgr;1 Expression , 2001, Stroke.

[19]  B. Brew,et al.  Quinolinic acid upregulates chemokine production and chemokine receptor expression in astrocytes , 2003, Glia.

[20]  R. Ransohoff,et al.  TNF-alpha down-regulates CXCR4 expression in primary murine astrocytes. , 2001, Brain research.

[21]  D. Gruol,et al.  The chemokine CXCL10 modulates excitatory activity and intracellular calcium signaling in cultured hippocampal neurons , 2004, Journal of Neuroimmunology.

[22]  L. Eng,et al.  GFAP and Astrogliosis , 1994, Brain pathology.

[23]  F. Eusebi,et al.  CXC chemokines interleukin-8 (IL-8) and growth-related gene product alpha (GROalpha) modulate Purkinje neuron activity in mouse cerebellum. , 1998, Journal of neuroimmunology.

[24]  M. Graeber,et al.  Neuronal MCP-1 Expression in Response to Remote Nerve Injury , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  W. Rostène,et al.  Neuroanatomical distribution of CXCR4 in adult rat brain and its localization in cholinergic and dopaminergic neurons , 2002, The European journal of neuroscience.

[26]  J. Meldolesi,et al.  Astrocytes, from brain glue to communication elements: the revolution continues , 2005, Nature Reviews Neuroscience.

[27]  Y. Matsumoto,et al.  Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis , 2006, Acta Neuropathologica.

[28]  P. Gierschik,et al.  Interleukin-6 and cAMP Induce Stromal Cell-derived Factor-1 Chemotaxis in Astroglia by Up-regulating CXCR4 Cell Surface Expression , 2002, The Journal of Biological Chemistry.

[29]  W. Rostène,et al.  Constitutive expression of CCR2 chemokine receptor and inhibition by MCP‐1/CCL2 of GABA‐induced currents in spinal cord neurones , 2005, Journal of neurochemistry.

[30]  R. Ransohoff,et al.  The expression and function of chemokines involved in CNS inflammation. , 2006, Trends in pharmacological sciences.

[31]  Bernhard Moser,et al.  Lymphocyte traffic control by chemokines , 2001, Nature Immunology.

[32]  H. Kettenmann,et al.  Secondary Lymphoid Tissue Chemokine (CCL21) Activates CXCR3 to Trigger a Cl− Current and Chemotaxis in Murine Microglia1 , 2002, The Journal of Immunology.

[33]  E. Lavi,et al.  Immunohistochemical analysis of CCR2, CCR3, CCR5, and CXCR4 in the human brain: potential mechanisms for HIV dementia. , 2000, Experimental and molecular pathology.

[34]  A. Lackner,et al.  Developmental expression patterns of CCR5 and CXCR4 in the rhesus macaque brain , 2002, Journal of Neuroimmunology.

[35]  J. Pachter,et al.  Expression of binding sites for beta chemokines on human astrocytes. , 1999, Glia.

[36]  G. Fan,et al.  Macrophage Inflammatory Protein 2 Inhibits β-Amyloid Peptide (1-42)-Mediated Hippocampal Neuronal Apoptosis through Activation of Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Signaling Pathways , 2005, Molecular Pharmacology.

[37]  G. Tarozzo,et al.  Expression of fractalkine and its receptor, CX3CR1, in response to ischaemia‐reperfusion brain injury in the rat , 2002, The European journal of neuroscience.

[38]  D. Kolson,et al.  CXCR3 expression in human central nervous system diseases , 2001, Neuropathology and applied neurobiology.

[39]  F. Eusebi,et al.  CXC chemokines interleukin-8 (IL-8) and growth-related gene product α (GROα) modulate Purkinje neuron activity in mouse cerebellum , 1998, Journal of Neuroimmunology.

[40]  R. Ransohoff,et al.  TNF-α mediates SDF-1α–induced NF-κB activation and cytotoxic effects in primary astrocytes , 2001 .

[41]  F. Aloisi,et al.  Lymphoid neogenesis in chronic inflammatory diseases , 2006, Nature Reviews Immunology.

[42]  J. Gutiérrez-Ramos,et al.  Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation , 1997, Nature.

[43]  A. Zlotnik Involvement of chemokine receptors in organ-specific metastasis. , 2006, Contributions to microbiology.

[44]  E. Major,et al.  Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors. , 1999, Virology.

[45]  M. Kaul,et al.  HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection , 2007, Cell Death and Differentiation.

[46]  M. Woodroofe,et al.  Chemokines induce migration and changes in actin polymerization in adult rat brain microglia and a human fetal microglial cell line in vitro , 1999, Journal of neuroscience research.

[47]  Wei Li,et al.  Different Neurotropic Pathogens Elicit Neurotoxic CCR9- or Neurosupportive CXCR3-Expressing Microglia1 , 2006, The Journal of Immunology.

[48]  Mario Mellado,et al.  Chemokine receptor homo‐ or heterodimerization activates distinct signaling pathways , 2001, The EMBO journal.

[49]  N. Rao,et al.  Upregulation of chemokine expression in the retinal vasculature in ischemia-reperfusion injury. , 2003, Investigative ophthalmology & visual science.

[50]  P. Murphy International Union of Pharmacology. XXX. Update on Chemokine Receptor Nomenclature , 2002, Pharmacological Reviews.

[51]  Brian D. Ross,et al.  Experimental Gliosarcoma Induces Chemokine Receptor Expression in Rat Brain , 2000, Experimental Neurology.

[52]  M. Tardieu,et al.  Effects of SDF-1α and gp120IIIB on apoptotic pathways in SK-N-SH neuroblastoma cells , 2006, Neuroscience Letters.

[53]  J. Berman,et al.  MCP‐1 (CCL2) protects human neurons and astrocytes from NMDA or HIV‐tat‐induced apoptosis , 2003, Journal of neurochemistry.

[54]  R. LaMotte,et al.  Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[55]  W. Rostène,et al.  Stromal cell‐derived factor‐1α modulation of the excitability of rat substantia nigra dopaminergic neurones: presynaptic mechanisms , 2006, Journal of neurochemistry.

[56]  D. Huszar,et al.  Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury , 2002, Journal of Neuroimmunology.

[57]  H. Boddeke,et al.  Vesicle-Mediated Transport and Release of CCL21 in Endangered Neurons: A Possible Explanation for Microglia Activation Remote from a Primary Lesion , 2005, The Journal of Neuroscience.

[58]  R. Maki,et al.  Characterization of fractalkine in rat brain cells: migratory and activation signals for CX3CR-1-expressing microglia. , 1999, Journal of immunology.

[59]  R. Miller,et al.  Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[60]  R. Kennedy,et al.  Infection of baboon microglia with SIV-HIV recombinant viruses: role of CD4 and chemokine receptors. , 2002, AIDS research and human retroviruses.

[61]  H. Müller,et al.  Cloning and characterization of SDF‐1γ, a novel SDF‐1 chemokine transcript with developmentally regulated expression in the nervous system , 2000, The European journal of neuroscience.

[62]  N. Jochnowitz,et al.  Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the spinal cord of a rat model of neuropathic pain. , 2005, The journal of pain : official journal of the American Pain Society.

[63]  H. Kettenmann,et al.  Neuronal SLC (CCL21) expression: implications for the neuron-microglial signaling system. , 2002, Ernst Schering Research Foundation workshop.

[64]  C. Palmer,et al.  Interleukin-10 inhibits endotoxin-induced pro-inflammatory cytokines in microglial cell cultures , 2005, Journal of Neuroimmunology.

[65]  J. Pachter,et al.  Functional expression of CCR2 by human fetal astrocytes , 2002, Journal of neuroscience research.

[66]  N. Berman,et al.  Early and specific expression of Monocyte Chemoattractant Protein-1 in the thalamus induced by cortical injury 1 1 Published on the World Wide Web on 25 May 2000. , 2000, Brain Research.

[67]  T. Yue,et al.  Prolonged Expression of Interferon‐Inducible Protein‐10 in Ischemic Cortex After Permanent Occlusion of the Middle Cerebral Artery in Rat , 1998, Journal of neurochemistry.

[68]  M. Kaul,et al.  Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[69]  P. Kitabgi,et al.  The chemokine SDF-1 differentially regulates axonal elongation and branching in hippocampal neurons , 2005, Journal of Cell Science.

[70]  M. Gill,et al.  Human immunodeficiency virus type 1 Nef protein mediates neural cell death: a neurotoxic role for IP-10. , 2004, Virology.

[71]  K. Watson,et al.  Macrophage inflammatory protein 2 inhibits beta-amyloid peptide (1-42)-mediated hippocampal neuronal apoptosis through activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. , 2005, Molecular pharmacology.

[72]  T. Williams,et al.  Chemokines and their receptors in allergic disease. , 2006, The Journal of allergy and clinical immunology.

[73]  Ravikumar Aalinkeel,et al.  Morphine modulates chemokine gene regulation in normal human astrocytes. , 2005, Clinical immunology.

[74]  M. Leach,et al.  Central Nervous System Inflammation and Neurological Disease in Transgenic Mice Expressing the CC Chemokine CCL21 in Oligodendrocytes , 2002, The Journal of Immunology.

[75]  I. Everall,et al.  Expression of β‐chemokines and chemokine receptors in human fetal astrocyte and microglial co‐cultures: Potential role of chemokines in the developing CNS , 2002, Glia.

[76]  M. Dorf,et al.  Mouse astrocytes respond to the chemokines MCP‐1 and KC, but reverse transcriptase‐polymerase chain reaction does not detect mRNA for the KC or new MCP‐1 receptor , 1996, Journal of neuroscience research.

[77]  W. Rostène,et al.  Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain , 2002, Journal of neurochemistry.

[78]  G. Kollias,et al.  CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity , 2001, Nature Neuroscience.

[79]  R. Alon,et al.  Right on the spot , 2005, Thrombosis and Haemostasis.

[80]  Elias Lolis,et al.  Structure, function, and inhibition of chemokines. , 2002, Annual review of pharmacology and toxicology.

[81]  C. Trebst,et al.  Functional expression of CXCR3 in cultured mouse and human astrocytes and microglia , 2002, Neuroscience.

[82]  C. Carter,et al.  Fractalkine modulates TNF‐α secretion and neurotoxicity induced by microglial activation , 2000 .

[83]  V. Perry,et al.  Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS , 2002, Glia.

[84]  F. Scaravilli,et al.  Expression of CCR-5/CXCR-4 in spinal cord of patients with AIDS , 2001, Acta Neuropathologica.

[85]  H. Boddeke,et al.  Simvastatin affects cell motility and actin cytoskeleton distribution of microglia , 2006, Glia.

[86]  Michael Greenberg,et al.  Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1α is mediated by the chemokine receptor CXCR4 , 1998, Current Biology.

[87]  C. Achim,et al.  Chemokines and receptors in HIV encephalitis , 1998, AIDS.

[88]  Georg W. Kreutzberg,et al.  Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function , 1999, Brain Research Reviews.

[89]  C. Achim,et al.  Selective Neuronal Vulnerability in HIV Encephalitis , 1992, Journal of neuropathology and experimental neurology.

[90]  Jialin Zheng,et al.  Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia , 1999, Journal of Neuroimmunology.

[91]  Prahlad T. Ram,et al.  G Protein Pathways , 2002, Science.

[92]  C. Culmsee,et al.  A Dual Role for the SDF-1/CXCR4 Chemokine Receptor System in Adult Brain: Isoform-Selective Regulation of SDF-1 Expression Modulates CXCR4-Dependent Neuronal Plasticity and Cerebral Leukocyte Recruitment after Focal Ischemia , 2002, The Journal of Neuroscience.

[93]  T. Schall,et al.  Neuronal expression of fractalkine in the presence and absence of inflammation , 1998, FEBS letters.

[94]  S. Takashima,et al.  Developmental expression of monocyte chemoattractant protein-1 in the human cerebellum and brainstem , 1999, Brain and Development.

[95]  W. Streit,et al.  Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[96]  W. Gan,et al.  ATP mediates rapid microglial response to local brain injury in vivo , 2005, Nature Neuroscience.

[97]  M. Baba,et al.  HIV-1-infected macrophages induce astrogliosis by SDF-1alpha and matrix metalloproteinases. , 2005, Biochemical and biophysical research communications.

[98]  H. Boddeke,et al.  Cutting Edge: Activity of Human Adult Microglia in Response to CC Chemokine Ligand 211 , 2004, The Journal of Immunology.

[99]  J. Pachter,et al.  Expression of binding sites for β chemokines on human astrocytes , 1999 .

[100]  C. Yiannoutsos,et al.  SDF‐1α Is Expressed in Astrocytes and Neurons in the AIDS Dementia Complex: An In Vivo and In Vitro Study , 2003 .

[101]  Richard J. Miller,et al.  Regulation of calcium currents by chemokines and their receptors , 2002, Journal of Neuroimmunology.

[102]  P. Piccioli,et al.  Glial and Neuronal Cells Express Functional Chemokine Receptor CXCR4 and Its Natural Ligand Stromal Cell‐Derived Factor 1 , 1999, Journal of neurochemistry.

[103]  Y. Jee,et al.  Upregulation of monocyte chemotactic protein-1 and CC chemokine receptor 2 in the central nervous system is closely associated with relapse of autoimmune encephalomyelitis in Lewis rats , 2002, Journal of Neuroimmunology.

[104]  Steffen Jung,et al.  Control of microglial neurotoxicity by the fractalkine receptor , 2006, Nature Neuroscience.

[105]  G. Kreutzberg Microglia: a sensor for pathological events in the CNS , 1996, Trends in Neurosciences.

[106]  H. Xiong,et al.  HIV‐1 gp120 enhances giant depolarizing potentials via chemokine receptor CXCR4 in neonatal rat hippocampus , 2006, The European journal of neuroscience.

[107]  R. Ravid,et al.  CX3CL1 and CX3CR1 Expression in Human Brain Tissue: Noninflammatory Control versus Multiple Sclerosis , 2003, Journal of neuropathology and experimental neurology.

[108]  C. Palmer,et al.  Differential expression of chemokines and chemokine receptors during microglial activation and inhibition , 2004, Journal of Neuroimmunology.

[109]  A. Zlotnik,et al.  The biology of chemokines and their receptors. , 2000, Annual review of immunology.

[110]  T. Springer,et al.  Functional expression of the CXC-chemokine receptor-4/fusin on mouse microglial cells and astrocytes. , 1997, Journal of immunology.

[111]  Zuo-ping Xie,et al.  Frequency Modulation of Synchronized Ca2+ Spikes in Cultured Hippocampal Networks through G-Protein-Coupled Receptors , 2003, The Journal of Neuroscience.

[112]  S. Woodman,et al.  Chemokine and chemokine-receptor expression in human glial elements: induction by the HIV protein, Tat, and chemokine autoregulation. , 2000, The American journal of pathology.

[113]  M. Dorf,et al.  Alternate splicing of mouse fusin/CXC chemokine receptor-4: stromal cell-derived factor-1alpha is a ligand for both CXC chemokine receptor-4 isoforms. , 1997, Journal of immunology.

[114]  T. Nakagawa,et al.  Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain , 2004, Neuroscience Research.

[115]  W. Streit,et al.  Transforming growth factor-beta1 increases CXCR4 expression, stromal-derived factor-1alpha-stimulated signalling and human immunodeficiency virus-1 entry in human monocyte-derived macrophages. , 2005, Immunology.

[116]  M. Satoh,et al.  Expression of stromal cell-derived factor-1 and CXCR4 chemokine receptor mRNAs in cultured rat glial and neuronal cells , 1998, Neuroscience Research.

[117]  U. de Girolami,et al.  Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS. , 1998, The American journal of pathology.

[118]  J. Bénavidès,et al.  Fractalkine modulates TNF-alpha secretion and neurotoxicity induced by microglial activation. , 2000, Glia.

[119]  K. Biber,et al.  Functional expression of the fractalkine (CX3C) receptor and its regulation by lipopolysaccharide in rat microglia. , 1999, European journal of pharmacology.

[120]  E. De Clercq,et al.  Differential signalling of the chemokine receptor CXCR4 by stromal cell‐derived factor 1 and the HIV glycoprotein in rat neurons and astrocytes , 2000, The European journal of neuroscience.

[121]  B. Brew,et al.  Expression of chemokines and their receptors in human and simian astrocytes: evidence for a central role of TNF alpha and IFN gamma in CXCR4 and CCR5 modulation. , 2003, Glia.

[122]  C. Petito,et al.  Hippocampal Injury and Alterations in Neuronal Chemokine Co‐Receptor Expression in Patients With AIDS , 2001, Journal of neuropathology and experimental neurology.

[123]  J. Berman,et al.  HIV‐1 tat protein induces a migratory phenotype in human fetal microglia by a CCL2 (MCP‐1)‐dependent mechanism: Possible role in NeuroAIDS , 2005, Glia.

[124]  Jingwu Z. Zhang,et al.  N-Methyl-d-aspartate Attenuates CXCR2-Mediated Neuroprotection through Enhancing the Receptor Phosphorylation and Blocking the Receptor Recycling , 2005, Molecular Pharmacology.

[125]  U. V. von Andrian,et al.  Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. , 2004, Annual review of immunology.

[126]  J. Warren,et al.  Acute Excitotoxic Injury Induces Expression of Monocyte Chemoattractant Protein-1 and Its Receptor, CCR2, in Neonatal Rat Brain , 2000, Experimental Neurology.

[127]  S. Kunkel Through the looking glass: the diverse in vivo activities of chemokines. , 1999, The Journal of clinical investigation.

[128]  R. Ransohoff,et al.  TNF-α down-regulates CXCR4 expression in primary murine astrocytes , 2001, Brain Research.

[129]  D. Noonan,et al.  Cytokines and chemokines as regulators of angiogenesis in health and disease. , 2006, Current pharmaceutical design.

[130]  W. Streit,et al.  Chemokine receptor expression in cultured glia and rat experimental allergic encephalomyelitis , 1998, Journal of Neuroimmunology.

[131]  I. Allaeys,et al.  Stromal cell‐derived factor‐1α directly modulates voltage‐dependent currents of the action potential in mammalian neuronal cells , 2005, Journal of neurochemistry.

[132]  C. Gerard,et al.  Chemokines: back to the future? , 2001, Nature Cell Biology.

[133]  M. Tardieu,et al.  Cellular expression of functional chemokine receptor CCR5 and CXCR4 in human embryonic neurons , 2001, Neuroscience Letters.

[134]  W. Rostène,et al.  Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: Functional effect of MCP‐1/CCL2 on calcium mobilization in primary cultured neurons , 2005, The Journal of comparative neurology.

[135]  W. Streit,et al.  Reactive microgliosis , 1999, Progress in Neurobiology.

[136]  G. Nisticó,et al.  gp120 Induces Cell Death in Human Neuroblastoma Cells Through the CXCR4 and CCR5 Chemokine Receptors , 2000, Journal of neurochemistry.

[137]  M. Tardieu,et al.  Human cytomegalovirus infection reduces surface CCR5 expression in human microglial cells, astrocytes and monocyte-derived macrophages. , 2002, Microbes and infection.

[138]  K. Frei,et al.  Toxoplasma gondii Infection of Neurons Induces Neuronal Cytokine and Chemokine Production, but Gamma Interferon- and Tumor Necrosis Factor-Stimulated Neurons Fail To Inhibit the Invasion and Growth of T. gondii , 2001, Infection and Immunity.

[139]  I. Romero,et al.  Regulation of chemokine receptor expression in human microglia and astrocytes , 2003, Journal of Neuroimmunology.

[140]  Wei Zhang,et al.  CXCR-4 (Fusin), a co-receptor for the type 1 human immunodeficiency virus (HIV-1), is expressed in the human brain in a variety of cell types, including microglia and neurons. , 1997, The American journal of pathology.

[141]  R. Ransohoff,et al.  Monocyte chemoattractant protein (MCP)-1 is rapidly expressed by sympathetic ganglion neurons following axonal injury , 2001, Neuroreport.

[142]  T. Town,et al.  Journal of Neuroinflammation BioMed Central Review Involvement of β-chemokines in the development of inflammatory demyelination , 2005 .

[143]  P. Kitabgi,et al.  Complex effects of stromal cell‐derived factor‐1α on melanin‐concentrating hormone neuron excitability , 2005, The European journal of neuroscience.

[144]  B. Hyman,et al.  Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer's disease brains. , 1998, The American journal of pathology.

[145]  F. Eusebi,et al.  Fractalkine/CX3CL1 depresses central synaptic transmission in mouse hippocampal slices , 2006, Neuropharmacology.

[146]  G. Siggins,et al.  Acute exposure to CXC chemokine ligand 10, but not its chronic astroglial production, alters synaptic plasticity in mouse hippocampal slices , 2004, Journal of Neuroimmunology.

[147]  Manuel Buttini,et al.  Cultured rat microglia express functional beta-chemokine receptors. , 1999, Journal of neuroimmunology.

[148]  B. Brew,et al.  Quinolinic acid up-regulates chemokine production and chemokine receptor expression in astrocytes. , 2003, Advances in experimental medicine and biology.

[149]  J. Abrams,et al.  Fractalkine protein localization and gene expression in mouse brain , 2003, Journal of neuroscience research.

[150]  R. Miledi,et al.  The chemokine growth-related gene product β protects rat cerebellar granule cells from apoptotic cell death through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors , 2000 .

[151]  R. Klein,et al.  Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS. , 1999, Journal of immunology.

[152]  K. Moores,et al.  Fractalkine Cleavage from Neuronal Membranes Represents an Acute Event in the Inflammatory Response to Excitotoxic Brain Damage , 2000, The Journal of Neuroscience.

[153]  A. Akaike,et al.  Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia? , 1998, FEBS letters.

[154]  H. Rittner,et al.  Chemokines and pain. , 2006, Current opinion in investigational drugs.

[155]  S. Appel,et al.  The chemokine MCP-1 and the dendritic and myeloid cells it attracts are increased in the mSOD1 mouse model of ALS , 2006, Molecular and Cellular Neuroscience.

[156]  G. Rall,et al.  Measles Virus Infection Induces Chemokine Synthesis by Neurons 1 , 2003, The Journal of Immunology.

[157]  Sandra A. Kinnear,et al.  Neuronal Fractalkine Expression in HIV-1 Encephalitis: Roles for Macrophage Recruitment and Neuroprotection in the Central Nervous System1 , 2000, The Journal of Immunology.

[158]  R J Miller,et al.  Chemokines and Glycoprotein120 Produce Pain Hypersensitivity by Directly Exciting Primary Nociceptive Neurons , 2001, The Journal of Neuroscience.

[159]  R. Ransohoff Snip-snip, kill-kill: truncated SDF-1 and HIV-associated neurodegeneration , 2003, Nature Neuroscience.

[160]  R. Ransohoff,et al.  The many roles of chemokines and chemokine receptors in inflammation. , 2006, The New England journal of medicine.

[161]  S. Maier,et al.  Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions , 2004, The European journal of neuroscience.

[162]  A. Copani,et al.  Neuroprotective activity of chemokines against N-methyl-D-aspartate or beta-amyloid-induced toxicity in culture. , 2000, European journal of pharmacology.

[163]  C. Mackay,et al.  Chemokines: immunology's high impact factors , 2001, Nature Immunology.

[164]  J. Szaflarski,et al.  Hypoxic-Ischemic Injury Induces Monocyte Chemoattractant Protein-1 Expression in Neonatal Rat Brain , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[165]  M. Lipp,et al.  Concerted action of the chemokine and lymphotoxin system in secondary lymphoid-organ development. , 2003, Current opinion in immunology.

[166]  F. Balkwill,et al.  The molecular and cellular biology of the chemokines , 1998, Journal of viral hepatitis.

[167]  Francesca Aloisi,et al.  Chemokines and Glial Cells: A Complex Network in the Central Nervous System , 2004, Neurochemical Research.

[168]  Takayuki Itoh,et al.  Microglia Express CCR5, CXCR4, and CCR3, but of These, CCR5 Is the Principal Coreceptor for Human Immunodeficiency Virus Type 1 Dementia Isolates , 1999, Journal of Virology.

[169]  H. Lassmann,et al.  CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin , 2005, Journal of Neuroinflammation.

[170]  P. Piccioli,et al.  Stromal cell‐derived factor‐1α induces astrocyte proliferation through the activation of extracellular signal‐regulated kinases 1/2 pathway , 2001, Journal of neurochemistry.

[171]  J. Newcombe,et al.  Expression of the interferon‐γ‐inducible chemokines IP‐10 and Mig and their receptor, CXCR3, in multiple sclerosis lesions , 2000, Neuropathology and applied neurobiology.

[172]  J. Freyssinet,et al.  Fractalkine reduces N‐methyl‐d‐aspartate‐induced calcium flux and apoptosis in human neurons through extracellular signal‐regulated kinase activation , 2004, The European journal of neuroscience.

[173]  M. Diamond,et al.  Neuronal CXCL10 Directs CD8+ T-Cell Recruitment and Control of West Nile Virus Encephalitis , 2005, Journal of Virology.

[174]  David Pinson,et al.  CXCL10‐induced cell death in neurons: role of calcium dysregulation , 2006, The European journal of neuroscience.

[175]  W. Rostène,et al.  Highly regionalized neuronal expression of monocyte chemoattractant protein‐1 (MCP‐1/CCL2) in rat brain: Evidence for its colocalization with neurotransmitters and neuropeptides , 2005, The Journal of comparative neurology.

[176]  Richard J. Miller,et al.  Chemokine receptors in the brain: A developing story , 2003, The Journal of comparative neurology.

[177]  Richard J. Miller,et al.  Electrophysiological analysis of neuronal chemokine receptors. , 2003, Methods.

[178]  J. G. Netzeband,et al.  The chemokine CCL2 modulates Ca2+ dynamics and electrophysiological properties of cultured cerebellar Purkinje neurons , 2005, The European journal of neuroscience.

[179]  E. Appella,et al.  Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[180]  A. Gad,et al.  RANTES promotes growth and survival of human first-trimester forebrain astrocytes , 2001, Nature Cell Biology.

[181]  F. Helmchen,et al.  Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo , 2005, Science.

[182]  A. Sauter,et al.  Ischemia‐induced neuronal expression of the microglia attracting chemokine secondary lymphoid‐tissue chemokine (SLC) , 2001, Glia.

[183]  F. Eusebi,et al.  Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity , 2005, Journal of Neuroimmunology.

[184]  R. Doms,et al.  Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons , 2000, Neuroscience.

[185]  T. Jessell,et al.  A Cxcl12-Cxcr4 Chemokine Signaling Pathway Defines the Initial Trajectory of Mammalian Motor Axons , 2005, Neuron.

[186]  M. Danik,et al.  The chemokine interleukin‐8 acutely reduces Ca2+ currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs , 2001, Journal of neurochemistry.

[187]  K. Fung,et al.  Expression Pattern of CXCR3, CXCR4, and CCR3 Chemokine Receptors in the Developing Human Brain , 2001, Journal of neuropathology and experimental neurology.

[188]  W. Streit,et al.  Transforming growth factor‐β1 increases CXCR4 expression, stromal‐derived factor‐1α‐stimulated signalling and human immunodeficiency virus‐1 entry in human monocyte‐derived macrophages , 2005 .

[189]  M. Baggiolini Chemokines and leukocyte traffic , 1998, Nature.

[190]  H. Xiong,et al.  Human immunodeficiency virus type 1 gp120 inhibits long‐term potentiation via chemokine receptor CXCR4 in rat hippocampal slices , 2006, Journal of neuroscience research.

[191]  J. Newcombe,et al.  Expression of the β-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue , 2000, Journal of Neuroimmunology.

[192]  E. Masliah Role of amyloid precursor protein in the mechanisms of neurodegeneration in Alzheimer's disease. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[193]  I. Bechmann,et al.  CXCR3-Dependent Microglial Recruitment Is Essential for Dendrite Loss after Brain Lesion , 2004, The Journal of Neuroscience.

[194]  V. Puri,et al.  Effects of Oestrogen on Trigeminal Ganglia in Culture: Implications for Hormonal Effects on Migraine , 2006, Cephalalgia : an international journal of headache.

[195]  R. Banati Brain plasticity and microglia: is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation? , 2002, Journal of Physiology-Paris.

[196]  H. Gendelman,et al.  Neuronal injury regulates fractalkine: relevance for HIV-1 associated dementia , 2003, Journal of Neuroimmunology.

[197]  Darrell R. Abernethy,et al.  International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels , 2003, Pharmacological Reviews.

[198]  Richard J. Miller,et al.  Expression of functional chemokine receptors by rat cerebellar neurons , 2002, Journal of Neuroimmunology.

[199]  A. Bachis,et al.  The chemokine receptor CXCR4 and not the N‐methyl‐D‐aspartate receptor mediates gp120 neurotoxicity in cerebellar granule cells , 2004, Journal of neuroscience research.

[200]  F. Eusebi,et al.  SDF‐1α‐mediated modulation of synaptic transmission in rat cerebellum , 2000 .

[201]  I. Franceschini,et al.  Developmental pattern of expression of the alpha chemokine stromal cell‐derived factor 1 in the rat central nervous system , 2001, The European journal of neuroscience.

[202]  B. Hyman,et al.  Immunohistochemical Study of the β-Chemokine Receptors CCR3 and CCR5 and Their Ligands in Normal and Alzheimer's Disease Brains , 1998 .

[203]  R. Ransohoff,et al.  TNF-alpha mediates SDF-1 alpha-induced NF-kappa B activation and cytotoxic effects in primary astrocytes. , 2001, The Journal of clinical investigation.

[204]  C. Overall,et al.  HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration , 2003, Nature Neuroscience.

[205]  W. Ye,et al.  Monocyte chemoattractant protein-1 expressed in neurons and astrocytes during focal ischemia in mice , 2001, Brain Research.

[206]  A. Nagai,et al.  Fractalkine and fractalkine receptors in human neurons and glial cells , 2002, Journal of neuroscience research.

[207]  K. Bacon,et al.  The Chemokine Fractalkine Inhibits Fas-Mediated Cell Death of Brain Microglia , 2000, Journal of Immunology.

[208]  J. Hoxie,et al.  CD4-independent association between HIV-1 gp120 and CXCR4: functional chemokine receptors are expressed in human neurons , 1997, Current Biology.

[209]  N. Bresolin,et al.  Production of monocyte chemoattractant protein‐1 in amyotrophic lateral sclerosis , 2005, Muscle & nerve.

[210]  J. Mudgett,et al.  Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2 , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[211]  P. Kitabgi,et al.  Dendrite-selective redistribution of the chemokine receptor CXCR4 following agonist stimulation , 2006, Molecular and Cellular Neuroscience.

[212]  D. Ho,et al.  In Vivo Distribution of the Human Immunodeficiency Virus/Simian Immunodeficiency Virus Coreceptors: CXCR4, CCR3, and CCR5 , 1998, Journal of Virology.

[213]  D. Kolson,et al.  Neuronal apoptosis is mediated by CXCL10 overexpression in simian human immunodeficiency virus encephalitis. , 2004, The American journal of pathology.

[214]  Karen L. Elkins,et al.  Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide , 1988, Nature.

[215]  B. Hyman,et al.  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 , 2000, Journal of Neuroimmunology.

[216]  F. Fahrenholz,et al.  The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. , 2003, Blood.

[217]  N. Berman,et al.  Ablation of the chemokine monocyte chemoattractant protein-1 delays retrograde neuronal degeneration, attenuates microglial activation, and alters expression of cell death molecules. , 2002, Brain research. Molecular brain research.

[218]  C. Yiannoutsos,et al.  SDF-1alpha is expressed in astrocytes and neurons in the AIDS dementia complex: an in vivo and in vitro study. , 2003, Journal of neuropathology and experimental neurology.

[219]  F. Eusebi,et al.  Stimulation of chemokine CXC receptor 4 induces synaptic depression of evoked parallel fibers inputs onto Purkinje neurons in mouse cerebellum , 2002, Journal of Neuroimmunology.

[220]  W. Rostène,et al.  The chemokine SDF-1/CXCL12 modulates the firing pattern of vasopressin neurons and counteracts induced vasopressin release through CXCR4. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[221]  R. Miledi,et al.  The chemokine growth-related gene product beta protects rat cerebellar granule cells from apoptotic cell death through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[222]  R. Miller,et al.  Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[223]  Y. Koninck,et al.  Spatial and temporal relationship between monocyte chemoattractant protein‐1 expression and spinal glial activation following peripheral nerve injury , 2006, Journal of neurochemistry.