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CXCR4 and CXCL12 Expression is Increased in the Nigro-Striatal System of Parkinson’s Disease

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Abstract

Except for a handful of inherited cases related to known gene defects, Parkinson’s disease (PD) is a sporadic neurodegenerative disease of unknown etiology. There is increasing evidence that inflammation and proliferation of microglia may contribute to the neuronal damage seen in the nigro-striatal dopaminergic system of PD patients. Microglia events that participate in neuronal injury include the release of pro-inflammatory and neurotoxic factors. Characterizing these factors may help to prevent the exacerbation of PD symptoms or to remediate the disease progression. In rodents, the nigro-striatal system exhibits high expression of the chemokine receptor CXCR4. Its natural ligand CXCL12 can promote neuronal apoptosis. Therefore, the present study investigated the expression of CXCR4 and CXCL12 in post-mortem brains of PD and control (non-PD) individuals and in an animal model of PD. In the human substantia nigra (SN), CXCR4 immunoreactivity was high in dopaminergic neurons. Interestingly, the SN of PD subjects exhibited higher expression of CXCR4 expression and CXCL12 than control subjects despite the loss of dopamine (DA) neurons. This effect was accompanied by an increase in activated microglia. However, results from post-mortem brains may not provide indication as to whether CXCL12/CXCR4 can cause the degeneration of DA neurons. To examine the role of these chemokines, we determined the levels of CXCL12 and CXCR4 in the SN of MPTP-treated mice. MPTP produced a time-dependent up-regulation of CXCR4 that preceded the loss of DA neurons. These results suggest that CXCL12/CXCR4 may participate in the etiology of PD and indicate a new possible target molecule for PD.

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References

  • Abi-Younes S, Sauty A, Mach F, Sukhova GK, Libby P, Luster AD (2000) The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques. Circ Res 86:131–138

    PubMed  CAS  Google Scholar 

  • Ahmed F, Tessarollo L, Thiele C, Mocchetti I (2008) Brain-derived neurotrophic factor modulates expression of chemokine receptors in the brain. Brain Res 1227:1–11

    Article  PubMed  CAS  Google Scholar 

  • Akiyama H, McGeer PL (1989) Microglial response to 6-hydroxydopamine-induced substantia nigra lesions. Brain Res 489:247–253

    Article  PubMed  CAS  Google Scholar 

  • Altar CA, Boylan CB, Jackson C, Hershenson S, Miller J, Wiegand SJ, Lindsay RM, Hyman C (1992) Brain-derived neurotrophic factor augments rotational behavior and nigrostriatal dopamine turnover in vivo. Proc Natl Acad Sci USA 89:11347–11351

    Article  PubMed  CAS  Google Scholar 

  • Anderson DW, Bradbury KA, Schneider JS (2006) Neuroprotection in Parkinson models varies with toxin administration protocol. Eur J Neurosci 24:3174–3182

    Article  PubMed  Google Scholar 

  • Asensio VC, Campbell IL (1999) Chemokines in the CNS: plurifunctional mediators in diverse states. Trends Neurosci 22:504–512

    Article  PubMed  CAS  Google Scholar 

  • Bachis A, Mocchetti I (2004) The chemokine receptor CXCR4 and not the N-methyl-D-aspartate receptor mediates gp120 neurotoxicity in cerebellar granule cells. J Neurosci Res 75:75–82

    Article  PubMed  CAS  Google Scholar 

  • Bachis A, Mocchetti I (2005) Brain-derived neurotrophic factor is neuroprotective against human immunodeficiency virus-1 envelope proteins. Ann NY Acad Sci 1053:247–257

    Article  PubMed  CAS  Google Scholar 

  • Bachis A, Aden SA, Nosheny RL, Andrews PM, Mocchetti I (2006) Axonal transport of human immunodeficiency virus type 1 envelope glycoprotein 120 is found in association with neuronal apoptosis. J Neurosci 26:6771–6780

    Article  PubMed  CAS  Google Scholar 

  • Banisadr G, Fontanges P, Haour F, Kitabgi P, Rostene W, Parsadaniantz SM (2002) Neuroanatomical distribution of CXCR4 in adult rat brain and its localization in cholinergic and dopaminergic neurons. Eur J Neurosci 16:1661–1671

    Article  PubMed  Google Scholar 

  • Berger JR, Arendt G (2000) HIV dementia: the role of the basal ganglia and dopaminergic systems. J Psychopharmacol 14:214–221

    Article  PubMed  CAS  Google Scholar 

  • Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E, Vescovi A, Bagetta G, Kollias G, Meldolesi J, Volterra A (2001) CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci 4:702–710

    Article  PubMed  CAS  Google Scholar 

  • Boka G, Anglade P, Wallach D, Javoy-Agid F, Agid Y, Hirsch EC (1994) Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson’s disease. Neurosci Lett 172:151–154

    Article  PubMed  CAS  Google Scholar 

  • Bonneh-Barkay D, Reaney SH, Langston WJ, Di Monte DA (2005) Redox cycling of the herbicide paraquat in microglial cultures. Brain Res Mol Brain Res 134:52–56

    Article  PubMed  CAS  Google Scholar 

  • Bromley SK, Peterson DA, Gunn MD, Dustin ML (2000) Cutting edge: hierarchy of chemokine receptor and TCR signals regulating T cell migration and proliferation. J Immunol 165:15–19

    PubMed  CAS  Google Scholar 

  • Burman A, Haworth O, Bradfield P, Parsonage G, Filer A, Thomas AM, Amft N, Salmon M, Buckley CD (2005) The role of leukocyte-stromal interactions in chronic inflammatory joint disease. Joint Bone Spine 72:10–16

    Article  PubMed  Google Scholar 

  • Cai TQ, Wright SD (1996) Human leukocyte elastase is an endogenous ligand for the integrin CR3 (CD11b/CD18, Mac-1, alpha M beta 2) and modulates polymorphonuclear leukocyte adhesion. J Exp Med 184:1213–1223

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Zhang SM, Hernan MA, Schwarzschild MA, Willett WC, Colditz GA, Speizer FE, Ascherio A (2003) Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol 60:1059–1064

    Article  PubMed  Google Scholar 

  • Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A (2005) Nonsteroidal antiinflammatory drug use and the risk for Parkinson’s disease. Ann Neurol 58:963–967

    Article  PubMed  CAS  Google Scholar 

  • Cicchetti F, Brownell AL, Williams K, Chen YI, Livni E, Isacson O (2002) Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 15:991–998

    Article  PubMed  CAS  Google Scholar 

  • Everall IP, Hudson L, al-Sarraj S, Honavar M, Lantos P, Kerwin R (1995) Decreased expression of AMPA receptor messenger RNA and protein in AIDS: a model for HIV-associated neurotoxicity. Nat Med 1:1174–1178

    Article  PubMed  CAS  Google Scholar 

  • Evert BO, Vogt IR, Kindermann C, Ozimek L, de Vos RA, Brunt ER, Schmitt I, Klockgether T, Wullner U (2001) Inflammatory genes are upregulated in expanded ataxin-3-expressing cell lines and spinocerebellar ataxia type 3 brains. J Neurosci 21:5389–5396

    PubMed  CAS  Google Scholar 

  • Floyd RA (1999) Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 222:236–245

    Article  PubMed  CAS  Google Scholar 

  • Fox L, Alford M, Achim C, Mallory M, Masliah E (1997) Neurodegeneration of somatostatin-immunoreactive neurons in HIV encephalitis. J Neuropathol Exp Neurol 56:360–368

    Article  PubMed  CAS  Google Scholar 

  • Gamo K, Kiryu-Seo S, Konishi H, Aoki S, Matsushima K, Wada K, Kiyama H (2008) G-protein-coupled receptor screen reveals a role for chemokine receptor CCR5 in suppressing microglial neurotoxicity. J Neurosci 28:11980–11988

    Article  PubMed  CAS  Google Scholar 

  • Guyon A, Skrzydelski D, Rovère C, Apartis E, Rostène W, Kitabgi P, Mélik Parsadaniantz S, Nahon JL (2008) Stromal-cell-derived factor alpha/CXCL12 modulates high-threshold calcium currents in rat substantia nigra. Eur J Neurosci 28:862–870

    Article  PubMed  CAS  Google Scholar 

  • Hesselgesser J, Taub D, Baskar P, Greenberg M, Hoxie J, Kolson DL, Horuk R (1998) Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is mediated by the chemokine receptor CXCR4. Curr Biol 8:595–598

    Article  PubMed  CAS  Google Scholar 

  • Hirsch EC, Hunot S, Damier P, Faucheux B (1998) Glial cells and inflammation in Parkinson’s disease: a role in neurodegeneration? Ann Neurol 44:S115–S120

    PubMed  CAS  Google Scholar 

  • Hunot S, Dugas N, Faucheux B, Hartmann A, Tardieu M, Debre P, Agid Y, Dugas B, Hirsch EC (1999) FcepsilonRII/CD23 is expressed in Parkinson’s disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J Neurosci 19:3440–3447

    PubMed  CAS  Google Scholar 

  • Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350:230–232

    Article  PubMed  CAS  Google Scholar 

  • Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y (2003) Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol 106:518–526

    Article  PubMed  CAS  Google Scholar 

  • Itoh K, Mehraein P, Weis S (2000) Neuronal damage of the substantia nigra in HIV-1 infected brains. Acta Neuropathol (Berl) 99:376–384

    Article  CAS  Google Scholar 

  • Kaul M, Lipton SA (1999) Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc Natl Acad Sci USA 96:8212–8216

    Article  PubMed  CAS  Google Scholar 

  • Kim CH, Broxmeyer HE (1999) SLC/exodus2/6Ckine/TCA4 induces chemotaxis of hematopoietic progenitor cells: differential activity of ligands of CCR7, CXCR3, or CXCR4 in chemotaxis vs. suppression of progenitor proliferation. J Leukoc Biol 66:455–461

    PubMed  CAS  Google Scholar 

  • Koutsilieri E, Sopper S, Scheller C, ter Meulen V, Riederer P (2002) Parkinsonism in HIV dementia. J Neural Transm 109:767–775

    Article  PubMed  CAS  Google Scholar 

  • Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisakk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, Newcombe J, Hohlfeld R, Meinl E (2006) Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 129:200–211

    Article  PubMed  Google Scholar 

  • Kurkowska-Jastrzebska I, Wronska A, Kohutnicka M, Czlonkowski A, Czlonkowska A (1999) The inflammatory reaction following 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine intoxication in mouse. Exp Neurol 156:50–61

    Article  PubMed  CAS  Google Scholar 

  • Langford D, Sanders VJ, Mallory M, Kaul M, Masliah E (2002) Expression of stromal cell-derived factor 1alpha protein in HIV encephalitis. J Neuroimmunol 127:115–126

    Article  PubMed  CAS  Google Scholar 

  • Lavi E, Strizki JM, Ulrich AM, Zhang W, Fu L, Wang Q, O’Connor M, Hoxie JA, Gonzalez-Scarano F (1997) 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. Am J Pathol 151:1035–1042

    PubMed  CAS  Google Scholar 

  • Lavi E, Kolson DL, Ulrich AM, Fu L, Gonzalez-Scarano F (1998) Chemokine receptors in the human brain and their relationship to HIV infection. J Neurovirol 4:301–311

    Article  PubMed  CAS  Google Scholar 

  • Lieberam I, Agalliu D, Nagasawa T, Ericson J, Jessell TM (2005) A Cxcl12-CXCR4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons. Neuron 47:667–679

    Article  PubMed  CAS  Google Scholar 

  • Limatola C, Giovannelli A, Maggi L, Ragozzino D, Castellani L, Ciotti MT, Vacca F, Mercanti D, Santoni A, Eusebi F (2000) SDF-1alpha-mediated modulation of synaptic transmission in rat cerebellum. Eur J Neurosci 12:2497–2504

    Article  PubMed  CAS  Google Scholar 

  • Liu B, Hong JS (2003) Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 304:1–7

    Article  PubMed  CAS  Google Scholar 

  • Luna L (1992) Luna’s method for melanin pigment removal. In: Histopathological methods and color atlas of special stains and tissue artifacts. Johnson Printers, Downers Grove, IL, pp 356–357

  • Luster AD (1998) Chemokines–chemotactic cytokines that mediate inflammation. N Engl J Med 338:436–445

    Article  PubMed  CAS  Google Scholar 

  • McArthur JC (2004) HIV dementia: an evolving disease. J Neuroimmunol 157:3–10

    Article  PubMed  CAS  Google Scholar 

  • McCandless EE, Piccio L, Woerner BM, Schmidt RE, Rubin JB, Cross AH, Klein RS (2008) Pathological expression of CXCL12 at the blood-brain barrier correlates with severity of multiple sclerosis. Am J Pathol 172:799–808

    Article  PubMed  Google Scholar 

  • McGeer PL, McGeer EG (2004) Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci 1035:104–116

    Article  PubMed  CAS  Google Scholar 

  • Meucci O, Fatatis A, Simen AA, Bushell TJ, Gray PW, Miller RJ (1998) Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci USA 95:14500–14505

    Article  PubMed  CAS  Google Scholar 

  • Miller JT, Bartley JH, Wimborne HJ, Walker AL, Hess DC, Hill WD, Carroll JE (2005) The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury. BMC Neurosci 6:63

    Article  PubMed  CAS  Google Scholar 

  • Mocchetti I, Bachis A, Nosheny RL, Tanda GL (2007) Brain-derived neurotrophic factor expression in the substantia nigra does not change after lesions of dopaminergic neurons. Neurotox Res 12:135–143

    Article  PubMed  CAS  Google Scholar 

  • Mocchetti I, Bachis A, Masliah E (2008) Chemokine receptors and neurotrophic factors: potential therapy against aids dementia? J Neurosci Res 86:243–255

    Article  PubMed  CAS  Google Scholar 

  • Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T (1994) Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett 165:208–210

    Article  PubMed  CAS  Google Scholar 

  • Mogi M, Togari A, Kondo T, Mizuno Y, Komure O, Kuno S, Ichinose H, Nagatsu T (2000) Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from parkinsonian brain. J Neural Transm 107:335–341

    Article  PubMed  CAS  Google Scholar 

  • Nagatsu T, Mogi M, Ichinose H, Togari A (2000) Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm Suppl 60:277–290

    PubMed  Google Scholar 

  • Nath A, Berger J (2004) HIV dementia. Curr Treat Options Neurol 6:139–151

    Article  PubMed  Google Scholar 

  • Nosheny RL, Bachis A, Aden SA, De Bernardi MA, Mocchetti I (2006) Intrastriatal administration of human immunodeficiency virus-1 glycoprotein 120 reduces glial cell-line derived neurotrophic factor levels and causes apoptosis in the substantia nigra. J Neurobiol 66:1311–1321

    Article  PubMed  CAS  Google Scholar 

  • Nosheny RL, Amhed F, Yakovlev AG, Meyer EM, Ren K, Tessarollo L, Mocchetti I (2007) Brain-derived neurotrophic factor prevents the nigrostriatal degeneration induced by human immunodeficiency virus-1 glycoprotein 120 in vivo. Eur J Neurosci 25:2275–2284

    Article  PubMed  Google Scholar 

  • Ogura K, Ogawa M, Yoshida M (1994) Effects of ageing on microglia in the normal rat brain: immunohistochemical observations. Neuroreport 5:1224–1226

    PubMed  CAS  Google Scholar 

  • Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, Torizuka T (2005) Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol 57:168–175

    Article  PubMed  CAS  Google Scholar 

  • Pashenkov M, Soderstrom M, Link H (2003) Secondary lymphoid organ chemokines are elevated in the cerebrospinal fluid during central nervous system inflammation. J Neuroimmunol 135:154–160

    Article  PubMed  CAS  Google Scholar 

  • Perry VH, Matyszak MK, Fearn S (1993) Altered antigen expression of microglia in the aged rodent CNS. Glia 7:60–67

    Article  PubMed  CAS  Google Scholar 

  • Petito CK, Roberts B, Cantando JD, Rabinstein A, Duncan R (2001) Hippocampal injury and alterations in neuronal chemokine co-receptor expression in patients with AIDS. J Neuropathol Exp Neurol 60:377–385

    PubMed  CAS  Google Scholar 

  • Przedborski S, Jackson-Lewis V, Naini AB, Jakowec M, Petzinger G, Miller R, Akram M (2001) The parkinsonian toxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP): a technical review of its utility and safety. J Neurochem 76:1265–1274

    Article  PubMed  CAS  Google Scholar 

  • Raivich G, Jones LL, Werner A, Bluthmann H, Doetschmann T, Kreutzberg GW (1999) Molecular signals for glial activation: pro- and anti-inflammatory cytokines in the injured brain. Acta Neurochir Suppl 73:21–30

    PubMed  CAS  Google Scholar 

  • Reyes MG, Faraldi F, Senseng CS, Flowers C, Fariello R (1991) Nigral degeneration in acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 82:39–44

    Article  CAS  Google Scholar 

  • Rostasy K, Egles C, Chauhan A, Kneissl M, Bahrani P, Yiannoutsos C, Hunter DD, Nath A, Hedreen JC, Navia BA (2003) SDF-1alpha is expressed in astrocytes and neurons in the AIDS dementia complex: an in vivo and in vitro study. J Neuropathol Exp Neurol 62:617–626

    PubMed  CAS  Google Scholar 

  • Schuller U, Koch A, Hartmann W, Garre ML, Goodyer CG, Cama A, Sorensen N, Wiestler OD, Pietsch T (2005) Subtype-specific expression and genetic alterations of the chemokinereceptor gene CXCR4 in medulloblastomas. Int J Cancer 117:82–89

    Article  PubMed  CAS  Google Scholar 

  • Skrzydelski D, Guyon A, Daugé V, Rovère C, Apartis E, Kitabgi P, Nahon JL, Rostène W, Mélik Parsadaniantz M (2007) The chemokine stromal cell-derived factor-1/CXCL12 activates the nigrostriatal dopamine system. J Neurochem 102:1175–1183

    Article  PubMed  CAS  Google Scholar 

  • Szabo I, Chen XH, Xin L, Adler MW, Howard OM, Oppenheim JJ, Rogers TJ (2002) Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain. Proc Natl Acad Sci USA 99:10276–10281

    Article  PubMed  CAS  Google Scholar 

  • Tabakman R, Lecht S, Sephanova S, Arien-Zakay H, Lazarovici P (2004) Interactions between the cells of the immune and nervous system: neurotrophins as neuroprotection mediators in CNS injury. Prog Brain Res 146:387–401

    PubMed  CAS  Google Scholar 

  • Tatton NA (2000) Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson’s disease. Exp Neurol 166:29–43

    Article  PubMed  CAS  Google Scholar 

  • Tran PB, Miller RJ (2005) HIV-1, chemokines and neurogenesis. Neurotox Res 8:149–158

    Article  PubMed  CAS  Google Scholar 

  • van der Meer P, Ulrich AM, Gonzalez-Scarano F, Lavi E (2000) Immunohistochemical analysis of CCR2, CCR3, CCR5, and CXCR4 in the human brain: potential mechanisms for HIV dementia. Exp Mol Pathol 69:192–201

    Article  PubMed  CAS  Google Scholar 

  • Yang L, Jackson E, Woerner BM, Perry A, Piwnica-Worms D, Rubin JB (2007) Blocking CXCR4-mediated cyclic AMP suppression inhibits brain tumor growth in vivo. Cancer Res 67:651–658

    Article  PubMed  CAS  Google Scholar 

  • Zheng J, Thylin MR, Ghorpade A, Xiong H, Persidsky Y, Cotter R, Niemann D, Che M, Zeng YC, Gelbard HA, Shepard RB, Swartz JM, Gendelman HE (1999) Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia. J Neuroimmunol 98:185–200

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Support for this work has been provided by Renschler and Lathum foundations. Special thanks to the brain bank of Johns Hopkins University School of Medicine, Baltimore, MD and Columbia University, New York, NY for sharing post-mortem human tissue samples for our studies. We also thank Drs. Bogdan Stoica and Alan Faden for invaluable technical support with the Zeiss LSM510 Meta confocal microscope.

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  1. Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04, 3970 Reservoir Rd, NW, Box 571464, Washington, DC, 20057, USA

    Mika Shimoji & Italo Mocchetti

  2. Department of Neurology, NFP Center of Excellence Georgetown University Hospital, 3800 Reservoir Rd, NW, Washington, DC, 20007, USA

    Fernando Pagan & Edward B. Healton

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  1. Mika Shimoji
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Correspondence to Italo Mocchetti.

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Shimoji, M., Pagan, F., Healton, E.B. et al. CXCR4 and CXCL12 Expression is Increased in the Nigro-Striatal System of Parkinson’s Disease. Neurotox Res 16, 318–328 (2009). https://doi.org/10.1007/s12640-009-9076-3

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