Fractalkine/CX3CL1 protects striatal neurons from synergistic morphine and HIV-1 Tat-induced dendritic losses and death

Molecular Neurodegeneration

Kurt F Hauser⁵  Pamela E Knapp⁵  Daniel H Conrad³  Jamie L Sturgill³  Mary E Sorrell²  Yun-Kyung Hahn¹  Shiping Zou¹  Nazira El-Hage²  Masami Suzuki⁴ 

[1] Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, VA 23298-0709 USA;Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0613 USA;Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, VA 23298-0678 USA;Cancer Pathophysiology Division, National Cancer Center Research Institute (Tsukiji Campus), 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, JAPAN;Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA 2329-0310 USA

关键词: microglia;    cell death;    transgenic;    neuroAIDS;    glial cell;    drug abuse;    heroin;    opioid;    AIDS;   

Others  :  865512
DOI  :  10.1186/1750-1326-6-78

 received in 2010-10-29, accepted in 2011-11-17,  发布年份 2011

【 摘 要 】

Background

Fractalkine/CX₃CL1 and its cognate receptor CX₃CR1 are abundantly expressed in the CNS. Fractalkine is an unusual C-X3-C motif chemokine that is important in neuron-microglial communication, a co-receptor for HIV infection, and can be neuroprotective. To assess the effects of fractalkine on opiate-HIV interactive neurotoxicity, wild-type murine striatal neurons were co-cultured with mixed glia from the striata of wild-type or Cx3cr1 knockout mice ± HIV-1 Tat and/or morphine. Time-lapse digital images were continuously recorded at 20 min intervals for up to 72 h using computer-aided microscopy to track the same cells repeatedly.

Results

Co-exposure to Tat and morphine caused synergistic increases in neuron death, dendritic pruning, and microglial motility as previously reported. Exogenous fractalkine prevented synergistic Tat and morphine-induced dendritic losses and neuron death even though the inflammatory mediator TNF-α remained significantly elevated. Antibody blockade of CX₃CR1 mimicked the toxic effects of morphine plus Tat, but did not add to their toxicity; while fractalkine failed to protect wild-type neurons co-cultured with Cx₃cr1^-/--null glia against morphine and Tat toxicity. Exogenous fractalkine also normalized microglial motility, which is elevated by Tat and morphine co-exposure, presumably limiting microglial surveillance that may lead to toxic effects on neurons. Fractalkine immunofluorescence was expressed in neurons and to a lesser extent by other cell types, whereas CX₃CR1 immunoreactivity or GFP fluorescence in cells cultured from the striatum of Cx3cr1^-/- (Cx3cr1^GFP/GFP) mice were associated with microglia. Immunoblotting shows that fractalkine levels were unchanged following Tat and/or morphine exposure and there was no increase in released fractalkine as determined by ELISA. By contrast, CX₃CR1 protein levels were markedly downregulated.

Conclusions

The results suggest that deficits in fractalkine-CX₃CR1 signaling contribute to the synergistic neurotoxic effects of opioids and Tat. Importantly, exogenous fractalkine can selectively protect neurons from the injurious effects of chronic opioid-HIV-1 Tat co-exposure, and this suggests a potential therapeutic course for neuroAIDS. Although the cellular mechanisms underlying neuroprotection are not certain, findings that exogenous fractalkine reduces microglial motility and fails to protect neurons co-cultured with Cx3cr1^-/- mixed glia suggest that fractalkine may act by interfering with toxic microglial-neuron interactions.

【 授权许可】

   
2011 Suzuki et al; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Adler MW, Geller EB, Rogers TJ, Henderson EE, Eisenstein TK: Opioids, receptors, and immunity. Adv Exp Med Biol 1993, 335:13-20.
• [2]Kumar R, Orsoni S, Norman L, Verma AS, Tirado G, Giavedoni LD, Staprans S, Miller GM, Buch SJ, Kumar A: Chronic morphine exposure causes pronounced virus replication in cerebral compartment and accelerated onset of AIDS in SIV/SHIV-infected Indian rhesus macaques. Virology 2006, 354:192-206.
• [3]Peterson PK, Sharp BM, Gekker G, Portoghese PS, Sannerud K, Balfour HH Jr: Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures. AIDS 1990, 4:869-873.
• [4]Donahoe RM, Vlahov D: Opiates as potential cofactors in progression of HIV-1 infections to AIDS. J Neuroimmunol 1998, 83:77-87.
• [5]Carr DJJ, Serou M: Exogenous and endogenous opioids as biological response modifiers. Immunopharmacology 1995, 31:59-71.
• [6]Hauser KF, El-Hage N, Stiene-Martin A, Maragos WF, Nath A, Persidsky Y, Volsky DJ, Knapp PE: HIV-1 neuropathogenesis: Glial mechanisms revealed through substance abuse. J Neurochem 2007, 100:567-586.
• [7]Turchan-Cholewo J, Liu Y, Gartner S, Reid R, Jie C, Peng X, Chen KC, Chauhan A, Haughey N, Cutler R, et al.: Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: protection by diosgenin and L-deprenyl. Neurobiol Dis 2006, 23:109-119.
• [8]Hauser KF, El-Hage N, Buch S, Berger JR, Tyor WR, Nath A, Bruce-Keller AJ, Knapp PE: Molecular targets of opiate drug abuse in neuroAIDS. Neurotox Res 2005, 8:63-80.
• [9]Nath A, Hauser KF, Wojna V, Booze RM, Maragos W, Prendergast M, Cass W, Turchan JT: Molecular basis for interactions of HIV and drugs of abuse. J Acquir Immune Defic Syndr 2002, 31(Suppl 2):S62-S69.
• [10]Gurwell JA, Nath A, Sun Q, Zhang J, Martin KM, Chen Y, Hauser KF: Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro. Neuroscience 2001, 102:555-563.
• [11]Anthony IC, Arango JC, Stephens B, Simmonds P, Bell JE: The effects of illicit drugs on the HIV infected brain. Front Biosci 2008, 13:1294-1307.
• [12]Bell JE, Arango JC, Anthony IC: Neurobiology of multiple insults: HIV-1-associated brain disorders in those who use illicit drugs. J Neuroimmune Pharmacol 2006, 1:182-191.
• [13]Peterson PK, Molitor TW, Chao CC: The opioid-cytokine connection. J Neuroimmunol 1998, 83:63-69.
• [14]Chang SL, Wu GD, Patel NA, Vidal EL, Fiala M: The effects of interaction between morphine and interleukin-1 on the immune response. Adv Exp Med Biol 1998, 437:67-72.
• [15]El-Hage N, Bruce-Keller AJ, Knapp PE, Hauser KF: CCL5/RANTES gene deletion attenuates opioid-induced increases in glial CCL2/MCP-1 immunoreactivity and activation in HIV-1 Tat exposed mice. J Neuroimmune Pharmacol 2008, 3:275-285.
• [16]El-Hage N, Wu G, Wang J, Ambati J, Knapp PE, Reed JL, Bruce-Keller AJ, Hauser KF: HIV-1 Tat and opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokines. Glia 2006, 53:132-146.
• [17]El-Hage N, Gurwell JA, Singh IN, Knapp PE, Nath A, Hauser KF: Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 Tat. Glia 2005, 50:91-106.
• [18]Rogers TJ, Peterson PK: Opioid G protein-coupled receptors: signals at the crossroads of inflammation. Trends Immunol 2003, 24:116-121.
• [19]Szabo I, Wetzel MA, Zhang N, Steele AD, Kaminsky DE, Chen C, Liu-Chen LY, Bednar F, Henderson EE, Howard OM, et al.: Selective inactivation of CCR5 and decreased infectivity of R5 HIV-1 strains mediated by opioid-induced heterologous desensitization. J Leukoc Biol 2003, 74:1074-1082.
• [20]Parenty G, Appelbe S, Milligan G: CXCR2 chemokine receptor antagonism enhances DOP opioid receptor function via allosteric regulation of the CXCR2-DOP receptor heterodimer. Biochem J 2008, 412:245-256.
• [21]Pello OM, Martinez-Munoz L, Parrillas V, Serrano A, Rodriguez-Frade JM, Toro MJ, Lucas P, Monterrubio M, Martinez A, Mellado M: Ligand stabilization of CXCR4/delta-opioid receptor heterodimers reveals a mechanism for immune response regulation. Eur J Immunol 2008, 38:537-549.
• [22]Chen C, Li J, Bot G, Szabo I, Rogers TJ, Liu-Chen LY: Heterodimerization and cross-desensitization between the mu-opioid receptor and the chemokine CCR5 receptor. Eur J Pharmacol 2004, 483:175-186.
• [23]Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ: A new class of membrane-bound chemokine with a CX3C motif. Nature 1997, 385:640-644.
• [24]Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, et al.: Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 1997, 91:521-530.
• [25]Hughes PM, Botham MS, Frentzel S, Mir A, Perry VH: Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS. Glia 2002, 37:314-327.
• [26]Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW, Sher A, Littman DR: Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 2000, 20:4106-4114.
• [27]Rossi DL, Hardiman G, Copeland NG, Gilbert DJ, Jenkins N, Zlotnik A, Bazan JF: Cloning and characterization of a new type of mouse chemokine. Genomics 1998, 47:163-170.
• [28]Savarin-Vuaillat C, Ransohoff RM: Chemokines and chemokine receptors in neurological disease: raise, retain, or reduce? Neurotherapeutics 2007, 4:590-601.
• [29]Yang XP, Mattagajasingh S, Su S, Chen G, Cai Z, Fox-Talbot K, Irani K, Becker LC: Fractalkine upregulates intercellular adhesion molecule-1 in endothelial cells through CX3CR1 and the Jak Stat5 pathway. Circ Res 2007, 101:1001-1008.
• [30]Re DB, Przedborski S: Fractalkine: moving from chemotaxis to neuroprotection. Nat Neurosci 2006, 9:859-861.
• [31]Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM: Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1. J Biol Chem 1998, 273:23799-23804.
• [32]Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, Delfraissy JF, McDermott DH, Murphy PM, Debre P, et al.: Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1. Science 2000, 287:2274-2277.
• [33]Shimizu N, Tanaka A, Oue A, Mori T, Ohtsuki T, Apichartpiyakul C, Uchiumi H, Nojima Y, Hoshino H: Broad usage spectrum of G protein-coupled receptors as coreceptors by primary isolates of HIV. AIDS 2009, 27:761-769.
• [34]Becker Y: The spreading of HIV-1 infection in the human organism is caused by fractalkine trafficking of the infected lymphocytes--a review, hypothesis and implications for treatment. Virus Genes 2007, 34:93-109.
• [35]Nishiyori A, Minami M, Ohtani Y, Takami S, Yamamoto J, Kawaguchi N, Kume T, Akaike A, Satoh M: Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia? FEBS Lett 1998, 429:167-172.
• [36]Meucci O, Fatatis A, Simen AA, Miller RJ: Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. Proc Natl Acad Sci (USA) 2000, 97:8075-8080.
• [37]Ransohoff RM, Liu L, Cardona AE: Chemokines and chemokine receptors: multipurpose players in neuroinflammation. Int Rev Neurobiol 2007, 82:187-204.
• [38]Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, et al.: Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 2006, 9:917-924.
• [39]Tong N, Perry SW, Zhang Q, James HJ, Guo H, Brooks A, Bal H, Kinnear SA, Fine S, Epstein LG, et al.: Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system. J Immunol 2000, 164:1333-1339.
• [40]Fuhrmann M, Bittner T, Jung CK, Burgold S, Page RM, Mitteregger G, Haass C, LaFerla FM, Kretzschmar H, Herms J: Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nat Neurosci 2010, 13:411-413.
• [41]Erichsen D, Lopez AL, Peng H, Niemann D, Williams C, Bauer M, Morgello S, Cotter RL, Ryan LA, Ghorpade A, et al.: Neuronal injury regulates fractalkine: relevance for HIV-1 associated dementia. J Neuroimmunol 2003, 138:144-155.
• [42]Cotter R, Williams C, Ryan L, Erichsen D, Lopez A, Peng H, Zheng J: Fractalkine (CX3CL1) and brain inflammation: Implications for HIV-1-associated dementia. J Neurovirol 2002, 8:585-598.
• [43]Letendre SL, Zheng JC, Kaul M, Yiannoutsos CT, Ellis RJ, Taylor MJ, Marquie-Beck J, Navia B, HIV Neuroimaging Consortium: Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals. J Neurovirol 2011, 17:63-69.
• [44]Depboylu C, Eiden LE, Schafer MK, Reinhart TA, Mitsuya H, Schall TJ, Weihe E: Fractalkine expression in the rhesus monkey brain during lentivirus infection and its control by 6-chloro-2',3'-dideoxyguanosine. J Neuropathol Exp Neurol 2006, 65:1170-1180.
• [45]Foussat A, Bouchet-Delbos L, Berrebi D, Durand-Gasselin I, Coulomb-L'Hermine A, Krzysiek R, Galanaud P, Levy Y, Emilie D: Deregulation of the expression of the fractalkine/fractalkine receptor complex in HIV-1-infected patients. Blood 2001, 98:1678-1686.
• [46]Meucci O, Fatatis A, Simen AA, Bushell TJ, Gray PW, Miller RJ: Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci (USA) 1998, 95:14500-14505.
• [47]Lauro C, Catalano M, Trettel F, Mainiero F, Ciotti MT, Eusebi F, Limatola C: The chemokine CX3CL1 reduces migration and increases adhesion of neurons with mechanisms dependent on the beta1 integrin subunit. J Immunol 2006, 177:7599-7606.
• [48]Brake DA, Debouck C, Biesecker G: Identification of an Arg-Gly-Asp (RGD) cell adhesion site in human immunodeficiency virus type 1 transactivation protein, tat. J Cell Biol 1990, 111:1275-1281.
• [49]Barillari G, Gendelman R, Gallo RC, Ensoli B: The Tat protein of HIV, a growth factor for AIDS Kaposi sarcoma and cytokine activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence. Proc Natl Acad Sci (USA) 1993, 90:7941-7945.
• [50]Toschi E, Bacigalupo I, Strippoli R, Cereseto A, Falchi M, Chiozzini C, Nappi F, Sgadari C, Barillari G, Mainiero F, et al.: HIV-1 Tat Regulates Endothelial Cell Cycle Progression via Activation of the Ras/ERK MAPK Signaling Pathway. Mol Biol Cell 2006, 17:1985-1994.
• [51]Vogel BE, Lee S, Hildebrand A, Craig W, Pierschbacher MD, Wong-Stall F, Ruoslahti E: A novel integrin specificity exemplified by binding of the αvβ 5 integrin to the basic domain of the HIV Tat protein and vitronectin. J Cell Biol 1993, 121:461-468.
• [52]Chen X, Geller EB, Rogers TJ, Adler MW: The chemokine CX3CL1/fractalkine interferes with the antinociceptive effect induced by opioid agonists in the periaqueductal grey of rats. Brain Res 2007, 1153:52-57.
• [53]Johnston IN, Milligan ED, Wieseler-Frank J, Frank MG, Zapata V, Campisi J, Langer S, Martin D, Green P, Fleshner M, et al.: A role for proinflammatory cytokines and fractalkine in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine. J Neurosci 2004, 24:7353-7365.
• [54]Sheng WS, Hu S, Ni HT, Rock RB, Peterson PK: WIN55,212-2 Inhibits Production of CX3CL1 by Human Astrocytes: Involvement of p38 MAP Kinase. J Neuroimmune Pharmacol 2009, 4:244-248.
• [55]Thomas DM, Francescutti-Verbeem DM, Kuhn DM: Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling. J Neurochem 2008, 106:696-705.
• [56]Lindia JA, McGowan E, Jochnowitz N, Abbadie C: Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the spinal cord of a rat model of neuropathic pain. J Pain 2005, 6:434-438.
• [57]Garton KJ, Gough PJ, Blobel CP, Murphy G, Greaves DR, Dempsey PJ, Raines EW: Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1). J Biol Chem 2001, 276:37993-38001.
• [58]Croitoru-Lamoury J, Guillemin GJ, Dormont D, Brew BJ: Quinolinic acid up-regulates chemokine production and chemokine receptor expression in astrocytes. Adv Exp Med Biol 2003, 527:37-45.
• [59]Cook A, Hippensteel R, Shimizu S, Nicolai J, Fatatis A, Meucci O: Interactions between chemokines: regulation of fractalkine/CX3CL1 homeostasis by SDF/CXCL12 in cortical neurons. J Biol Chem 2010, 285:10563-10571.
• [60]Zou S, Fitting S, Hahn YK, Welch SP, El-Hage N, Hauser KF, Knapp PE: Morphine potentiates neurodegenerative effects of HIV-1 Tat through actions at μ-opioid receptor-expressing glia. Brain 2011, in press.
• [61]Singh IN, El-Hage N, Campbell ME, Lutz SE, Knapp PE, Nath A, Hauser KF: Differential involvement of p38 and JNK MAP kinases in HIV-1 Tat and gp120-induced apoptosis and neurite degeneration in striatal neurons. Neuroscience 2005, 135:781-790.
• [62]Singh IN, Goody RJ, Dean C, Ahmad NM, Lutz SE, Knapp PE, Nath A, Hauser KF: Apoptotic death of striatal neurons induced by HIV-1 Tat and gp120: differential involvement of caspase-3 and endonuclease G. J Neurovirol 2004, 10:141-151.
• [63]Zou S, El-Hage N, Podhaizer EM, Knapp PE, Hauser KF: PTEN gene silencing prevents HIV-1 gp120IIIB-induced degeneration of striatal neurons. J Neurovirol 2011, 17:41-49.
• [64]Bakalkin G, Watanabe H, Jezierska J, Depoorter C, Verschuuren-Bemelmans C, Bazov I, Artemenko KA, Yakovleva T, Dooijes D, et al.: Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. Am J Hum Genet 2010, 87:593-603.
• [65]Friedl P: Prespecification and plasticity: shifting mechanisms of cell migration. Curr Opin Cell Biol 2004, 16:14-23.
• [66]Inoue K: Purinergic systems in microglia. Cell Mol Life Sci 2008, 65:3074-3080.
• [67]Horvath RJ, Deleo JA: Morphine enhances microglial migration through modulation of P2X4 receptor signaling. J Neurosci 2009, 29:998-1005.
• [68]Luo Y, Berman MA, Abromson-Leeman SR, Dorf ME: Tumor necrosis factor is required for RANTES-induced astrocyte monocyte chemoattractant protein-1 production. Glia 2003, 43:119-127.
• [69]Benveniste EN, Benos DJ: TNF-alpha- and IFN-gamma-mediated signal transduction pathways: effects on glial cell gene expression and function. FASEB J 1995, 9:1577-1584.
• [70]El-Hage N, Bruce-Keller AJ, Yakovleva T, Bakalkin G, Knapp PE, Hauser KF: Morphine exacerbates HIV-1 Tat-induced cytokine production in astrocytes through convergent effects on [Ca2+]i, NF-κB trafficking and transcription. PLoS ONE 2008, 3:e4093.
• [71]Heinisch S, Palma J, Kirby LG: Interactions between chemokine and mu-opioid receptors: anatomical findings and electrophysiological studies in the rat periaqueductal grey. Brain Behav Immun 2011, 25:360-372.
• [72]Shan S, Hong-Min T, Yi F, Jun-Peng G, Yue F, Yan-Hong T, Yun-Ke Y, Wen-Wei L, Xiang-Yu W, Jun M, et al.: New evidences for fractalkine/CX3CL1 involved in substantia nigral microglial activation and behavioral changes in a rat model of Parkinson's disease. Neurobiol Aging 2011, 32:443-458.
• [73]Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, et al.: Synaptic pruning by microglia is necessary for normal brain development. Science 2011, 333:1456-1458.
• [74]Hundhausen C, Misztela D, Berkhout TA, Broadway N, Saftig P, Reiss K, Hartmann D, Fahrenholz F, Postina R, Matthews V, et al.: The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood 2003, 102:1186-1195.
• [75]Weskamp G, Ford JW, Sturgill J, Martin S, Docherty AJ, Swendeman S, Broadway N, Hartmann D, Saftig P, Umland S, et al.: ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23. Nat Immunol 2006, 7:1293-1298.
• [76]Hundhausen C, Schulte A, Schulz B, Andrzejewski MG, Schwarz N, von HP, Winter U, Paliga K, Reiss K, Saftig P, et al.: Regulated shedding of transmembrane chemokines by the disintegrin and metalloproteinase 10 facilitates detachment of adherent leukocytes. J Immunol 2007, 178:8064-8072.
• [77]Tsubota K, Nishiyama T, Mishima K, Inoue H, Doi T, Hattori Y, Kodama T, Higuchi A, Hayashi Y, Saito I: The role of fractalkine as an accelerating factor on the autoimmune exocrinopathy in mice. Invest Ophthalmol Vis Sci 2009, 50:4753-4760.
• [78]Wildenberg ME, van Helden-Meeuwsen CG, Drexhage HA, Versnel MA: Altered fractalkine cleavage potentially promotes local inflammation in NOD salivary gland. Arthritis Res Ther 2008, 10:R69. BioMed Central Full Text
• [79]Yang XP, Mattagajasingh S, Su S, Chen G, Cai Z, Fox-Talbot K, Irani K, Becker LC: Fractalkine upregulates intercellular adhesion molecule-1 in endothelial cells through CX3CR1 and the Jak Stat5 pathway. Circ Res 2007, 101:1001-1008.
• [80]Garin A, Tarantino N, Faure S, Daoudi M, Lecureuil C, Bourdais A, Debre P, Deterre P, Combadiere C: Two novel fully functional isoforms of CX3CR1 are potent HIV coreceptors. J Immunol 2003, 171:5305-5312.
• [81]Block ML, Zecca L, Hong JS: Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 2007, 8:57-69.
• [82]Cabral GA, Raborn ES, Griffin L, Dennis J, Marciano-Cabral F: CB2 receptors in the brain: role in central immune function. Br J Pharmacol 2008, 153:240-251.
• [83]Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC: CNS immune privilege: hiding in plain sight. Immunol Rev 2006, 213:48-65.
• [84]Gonzalez-Scarano F, Martin-Garcia J: The neuropathogenesis of AIDS. Nat Rev Immunol 2005, 5:69-81.
• [85]Gupta S, Knight AG, Gupta S, Knapp PE, Hauser KF, Keller JN, Bruce-Keller AJ: HIV-Tat elicits microglial glutamate release: role of NAPDH oxidase and the cystine-glutamate antiporter. Neurosci Lett 2010, 485:233-236.
• [86]Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW: CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS. J Neurosci 2006, 26:1098-1106.
• [87]Bhaskar K, Konerth M, Kokiko-Cochran ON, Cardona A, Ransohoff RM, Lamb BT: Regulation of tau pathology by the microglial fractalkine receptor. Neuron 2010, 68:19-31.
• [88]Zhuang ZY, Kawasaki Y, Tan PH, Wen YR, Huang J, Ji RR: Role of the CX3CR1/p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine. Brain Behav Immun 2007, 21:642-651.
• [89]Hulshof S, van Haastert ES, Kuipers HF, van den Elsen PJ, De Groot CJ, vand V, Ravid R, Biber K: CX3CL1 and CX3CR1 expression in human brain tissue: noninflammatory control versus multiple sclerosis. J Neuropathol Exp Neurol 2003, 62:899-907.
• [90]Yoshida H, Imaizumi T, Fujimoto K, Matsuo N, Kimura K, Cui X, Matsumiya T, Tanji K, Shibata T, Tamo W, et al.: Synergistic stimulation, by tumor necrosis factor-alpha and interferon-gamma, of fractalkine expression in human astrocytes. Neurosci Lett 2001, 303:132-136.
• [91]Denes A, Ferenczi S, Halasz J, Kornyei Z, Kovacs KJ: Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse. J Cereb Blood Flow Metab 2008, 28:1707-1721.
• [92]Conant K, Garzino-Demo A, Nath A, McArthur JC, Halliday W, Power C, Gallo RC, Major EO: Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia. Proc Natl Acad Sci (USA) 1998, 95:3117-3121.
• [93]Bruce-Keller AJ, Turchan-Cholewo J, Smart EJ, Guerin T, Chauhan A, Reid R, Xu R, Nath A, Knapp PE, Hauser KF: Morphine causes rapid increases in glial activation and neuronal injury in the striatum of inducible HIV-1 Tat transgenic mice. Glia 2008, 56:1414-1427.
• [94]Sholl DA: Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat (London) 1953, 87:387-407.
• [95]Hauser KF, McLaughlin PJ, Zagon IS: Endogenous opioid systems and the regulation of dendritic growth and spine formation. J Comp Neurol 1989, 281:13-22.