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Vesicular Integrity in Parkinson’s Disease

  • Movement Disorders (SA Factor, Section Editor)
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Abstract

The defining motor characteristics of Parkinson’s disease (PD) are mediated by the neurotransmitter dopamine (DA). Dopamine molecules spend most of their lifespan stored in intracellular vesicles awaiting release and very little time in the extracellular space or the cytosol. Without proper packaging of transmitter and trafficking of vesicles to the active zone, dopamine neurotransmission cannot occur. In the cytosol, dopamine is readily oxidized; excessive cytosolic dopamine oxidation may be pathogenic to nigral neurons in PD. Thus, factors that disrupt vesicular function may impair signaling and increase the vulnerability of dopamine neurons. This review outlines the many mechanisms by which disruption of vesicular function may contribute to the pathogenesis of PD. From direct inhibition of dopamine transport into vesicles by pharmacological or toxicological agents to alterations in vesicle trafficking by PD-related gene products, variations in the proper compartmentalization of dopamine can wreak havoc on a functional dopamine pathway. Findings from patient populations, imaging studies, transgenic models, and mechanistic studies will be presented to document the relationship between impaired vesicular function and vulnerability of the nigrostriatal dopamine system. Given the deleterious effects of impaired vesicular function, strategies aimed at enhancing vesicular function may be beneficial in the treatment of PD.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Zarow C, Lyness SA, Mortimer JA, Chui HC. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol. 2003;60(3):337–41.

    PubMed  Google Scholar 

  2. Halliday GM, Li YW, Blumbergs PC, Joh TH, Cotton RG, Howe PR, et al. Neuropathology of immunohistochemically identified brainstem neurons in Parkinson's disease. Ann Neurol. 1990;27(4):373–85. doi:10.1002/ana.410270405.

    PubMed  CAS  Google Scholar 

  3. Richman A, Tyhurst JS. An extrapyramidal syndrome with reserpine. Can Med Assoc J. 1955;72(6):457–8.

    PubMed  CAS  Google Scholar 

  4. Brodie BB, Shore PA, Silver SL. Potentiating action of chlorpromazine and reserpine. Nature. 1955;175(4469):1133–4.

    PubMed  CAS  Google Scholar 

  5. Pletscher A, Shore PA, Brodie BB. Serotonin release as a possible mechanism of reserpine action. Science. 1955;122(3165):374–5.

    PubMed  CAS  Google Scholar 

  6. Carlsson A, Lindqvist M, Magnusson T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature. 1957;180(4596):1200.

    PubMed  CAS  Google Scholar 

  7. Ehringer H. Hornykiewicz O [Distribution of noradrenaline and dopamine (3-hydroxytyramine) in the human brain and their behavior in diseases of the extrapyramidal system]. Klin Wochenschr. 1960;38:1236–9.

    PubMed  CAS  Google Scholar 

  8. Birkmayer W. Hornykiewicz O [The L-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia]. Wien Klin Wochenschr. 1961;73:787–8.

    PubMed  CAS  Google Scholar 

  9. Coughenour HD, Spaulding RS, Thompson CM. The synaptic vesicle proteome: a comparative study in membrane protein identification. Proteomics. 2004;4(10):3141–55. doi:10.1002/pmic.200300817.

    PubMed  CAS  Google Scholar 

  10. Blondeau F, Ritter B, Allaire PD, Wasiak S, Girard M, Hussain NK, et al. Tandem MS analysis of brain clathrin-coated vesicles reveals their critical involvement in synaptic vesicle recycling. Proc Natl Acad Sci U S A. 2004;101(11):3833–8. doi:10.1073/pnas.0308186101.

    PubMed  CAS  Google Scholar 

  11. Morciano M, Burre J, Corvey C, Karas M, Zimmermann H, Volknandt W. Immunoisolation of 2 synaptic vesicle pools from synaptosomes: a proteomics analysis. J Neurochem. 2005;95(6):1732–45. doi:10.1111/j.1471-4159.2005.03506.x.

    PubMed  CAS  Google Scholar 

  12. Burre J, Beckhaus T, Schagger H, Corvey C, Hofmann S, Karas M, et al. Analysis of the synaptic vesicle proteome using three gel-based protein separation techniques. Proteomics. 2006;6(23):6250–62. doi:10.1002/pmic.200600357.

    PubMed  CAS  Google Scholar 

  13. Takamori S, Holt M, Stenius K, Lemke EA, Gronborg M, Riedel D, et al. Molecular anatomy of a trafficking organelle. Cell. 2006;127(4):831–46. doi:10.1016/j.cell.2006.10.030.

    PubMed  CAS  Google Scholar 

  14. Liu YJ, Edwards RH. The role of vesicular transport proteins in synaptic transmission and neural degeneration. Annu Rev Neurosci. 1997;20:125–56.

    PubMed  CAS  Google Scholar 

  15. Edwards RH. The neurotransmitter cycle and quantal size. Neuron. 2007;55(6):835–58. doi:10.1016/j.neuron.2007.09.001.

    PubMed  CAS  Google Scholar 

  16. Chaudhry FA, Edwards RH, Fonnum F. Vesicular neurotransmitter transporters as targets for endogenous and exogenous toxic substances. Annu Rev Pharmacol Toxicol. 2008;48(1):277–301. doi:10.1146/annurev.pharmtox.46.120604.141146.

    PubMed  CAS  Google Scholar 

  17. Hannah MJ, Schmidt AA, Huttner WB. Synaptic vesicle biogenesis. Annu Rev Cell Dev Biol. 1999;15:733–98. doi:10.1146/annurev.cellbio.15.1.733.

    PubMed  CAS  Google Scholar 

  18. Sudhof TC. The synaptic vesicle cycle. Annu Rev Neurosci. 2004;27:509–47. doi:10.1146/annurev.neuro.26.041002.131412.

    PubMed  Google Scholar 

  19. Segovia M, Ales E, Montes MA, Bonifas I, Jemal I, Lindau M, et al. Push-and-pull regulation of the fusion pore by synaptotagmin-7. Proc Natl Acad Sci U S A. 2010;107(44):19032–7. doi:10.1073/pnas.1014070107.

    PubMed  CAS  Google Scholar 

  20. Schikorski T, Stevens CF. Quantitative ultrastructural analysis of hippocampal excitatory synapses. J Neurosci. 1997;17(15):5858–67.

    PubMed  CAS  Google Scholar 

  21. Murthy VN, Stevens CF. Reversal of synaptic vesicle docking at central synapses. Nat Neurosci. 1999;2(6):503–7. doi:10.1038/9149.

    PubMed  CAS  Google Scholar 

  22. Pyle JL, Kavalali ET, Piedras-Renteria ES, Tsien RW. Rapid reuse of readily releasable pool vesicles at hippocampal synapses. Neuron. 2000;28(1):221–31.

    PubMed  CAS  Google Scholar 

  23. Südhof TC. The synaptic vesiclecycle revisited. Neuron. 2000;28(2):317–20. doi:10.1016/s0896-6273(00)00109-4.

    PubMed  Google Scholar 

  24. Rizo J, Sudhof TC. The membrane fusion enigma: SNAREs, Sec1/Munc18 proteins, and their accomplices—guilty as charged? Annu Rev Cell Dev Biol. 2012;28:279–308. doi:10.1146/annurev-cellbio-101011-155818.

    PubMed  CAS  Google Scholar 

  25. Maximov A, Sudhof TC. Autonomous function of synaptotagmin 1 in triggering synchronous release independent of asynchronous release. Neuron. 2005;48(4):547–54. doi:10.1016/j.neuron.2005.09.006.

    PubMed  CAS  Google Scholar 

  26. Pang ZP, Sun J, Rizo J, Maximov A, Sudhof TC. Genetic analysis of synaptotagmin 2 in spontaneous and Ca2 + -triggered neurotransmitter release. EMBO J. 2006;25(10):2039–50. doi:10.1038/sj.emboj.7601103.

    PubMed  CAS  Google Scholar 

  27. Barker LA, Dowdall MJ, Whittaker VP. Choline metabolism in the cerebral cortex of guinea pigs. Stable-bound acetylcholine. Biochem J. 1972;130(4):1063–75.

    PubMed  CAS  Google Scholar 

  28. Ceccarelli B, Hurlbut WP. Vesicle hypothesis of the release of quanta of acetylcholine. Physiol Rev. 1980;60(2):396–441.

    PubMed  CAS  Google Scholar 

  29. Paisan-Ruiz C, Nath P, Washecka N, Gibbs JR, Singleton AB. Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls. Hum Mutat. 2008;29(4):485–90. doi:10.1002/humu.20668.

    PubMed  CAS  Google Scholar 

  30. Belluzzi E, Greggio E, Piccoli G. Presynaptic dysfunction in Parkinson's disease: a focus on LRRK2. Biochem Soc Trans. 2012;40(5):1111–6. doi:10.1042/BST20120124.

    PubMed  CAS  Google Scholar 

  31. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997;276(5321):2045–7.

    PubMed  CAS  Google Scholar 

  32. Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, et al. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet. 1998;18(2):106–8. doi:10.1038/ng0298-106.

    PubMed  CAS  Google Scholar 

  33. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, et al. Alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003;302(5646):841. doi:10.1126/science.1090278.

    PubMed  CAS  Google Scholar 

  34. Davidson WS, Jonas A, Clayton DF, George JM. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem. 1998;273(16):9443–9.

    PubMed  CAS  Google Scholar 

  35. • Scott D, Roy S. Alpha-Synuclein inhibits intersynaptic vesicle mobility and maintains recycling-pool homeostasis. J Neurosci. 2012;32(30):10129–35. doi:10.1523/jneurosci.0535–12.2012. Demonstrated that α-synuclein expression inversely correlates with synaptic vesicular trafficking and recycling pool size in hippocampal neurons.

    PubMed  CAS  Google Scholar 

  36. • Gaugler MN, Genc O, Bobela W, Mohanna S, Ardah MT, El-Agnaf OM, et al. Nigrostriatal overabundance of alpha-synuclein leads to decreased vesicle density and deficits in dopamine release that correlate with reduced motor activity. Acta Neuropathol. 2012;123(5):653–69. Demonstrated that α-synuclein overexpression inhibits vesicular trafficking in DA terminals, and causes parkinsonian pathology and motor effects in rats.

    PubMed  CAS  Google Scholar 

  37. Caughey B, Lansbury PT. Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu Rev Neurosci. 2003;26:267–98. doi:10.1146/annurev.neuro.26.010302.081142.

    PubMed  CAS  Google Scholar 

  38. Conway KA, Rochet J-C, Bieganski RM, Lansbury Jr PT. Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science. 2001;294(5545):1346.

    PubMed  CAS  Google Scholar 

  39. Rochet JC, Outeiro TF, Conway KA, Ding TT, Volles MJ, Lashuel HA, et al. Interactions among alpha-synuclein, dopamine, and biomembranes—some clues for understanding neurodegeneration in Parkinson's disease. J Mol Neurosci. 2004;23(1–2):23–33. doi:10.1385/jmn:23:1-2:023.

    PubMed  CAS  Google Scholar 

  40. Choi BK, Choi MG, Kim JY, Yang Y, Lai Y, Kweon DH, et al. Large alpha-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking. Proc Natl Acad Sci U S A. 2013. doi:10.1073/pnas.1218424110.

    Google Scholar 

  41. Volles MJ, Lee SJ, Rochet JC, Shtilerman MD, Ding TT, Kessler JC, et al. Vesicle permeabilization by protofibrillar alpha-synuclein: implications for the pathogenesis and treatment of Parkinson's disease. Biochemistry. 2001;40(26):7812–9. doi:10.1021/bi0102398.

    PubMed  CAS  Google Scholar 

  42. Eisenhofer G, Kopin IJ, Goldstein DS. Leaky catecholamine stores: undue waste or a stress response coping mechanism? Ann NY Acad Sci. 2004;1018(1):224–30. doi:10.1196/annals.1296.027.

    PubMed  CAS  Google Scholar 

  43. Uhl GR. Hypothesis: the role of dopaminergic transporters in selective vulnerability of cells in Parkinson's disease. Ann Neurol. 1998;43(5):555–60. doi:10.1002/ana.410430503.

    PubMed  CAS  Google Scholar 

  44. Miller GW, Gainetdinov RR, Levey AI, Caron MG. Dopamine transporters and neuronal injury. Trends Pharmacol Sci. 1999;20(10):424–9.

    PubMed  CAS  Google Scholar 

  45. Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004;56(3):331–49. doi:10.1124/pr.56.3.1.

    PubMed  CAS  Google Scholar 

  46. Burke WJ, Li SW, Chung HD, Ruggiero DA, Kristal BS, Johnson EM, et al. Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: role in neurodegenerative diseases. NeuroToxicol. 2004;25(1–2):101–15.

    CAS  Google Scholar 

  47. Rees JN, Florang VR, Eckert LL, Doorn JA. Protein reactivity of 3,4-Dihydroxyphenylacetaldehyde, a toxic dopamine metabolite, is dependent on both the aldehyde and the catechol. Chem Res Toxicol. 2009;22(7):1256–63. doi:10.1021/tx9000557.

    PubMed  CAS  Google Scholar 

  48. Wey MC, Fernandez E, Martinez PA, Sullivan P, Goldstein DS, Strong R. Neurodegeneration and motor dysfunction in mice lacking cytosolic and mitochondrial aldehyde dehydrogenases: implications for Parkinson's disease. PLoS One. 2012;7(2):e31522. doi:10.1371/journal.pone.0031522.

    PubMed  CAS  Google Scholar 

  49. Goldstein DS, Sullivan P, Holmes C, Kopin IJ, Basile MJ, Mash DC. Catechols in post-mortem brain of patients with Parkinson disease. Eur J Neurol. 2011;18(5):703–10. doi:10.1111/j.1468-1331.2010.03246.x.

    PubMed  CAS  Google Scholar 

  50. Graham DG, Tiffany SM, Bell WR, Gutknecht WF. Autoxidation versus covalent binding of quinones as mechanism of toxicity of dopamine, 6-Hydroxydopamine, and related compounds toward C1300-Neuroblastoma cells in vitro. Mol Pharmacol. 1978;14(4):644–53.

    PubMed  CAS  Google Scholar 

  51. Zahid M, Saeed M, Yang L, Beseler C, Rogan E, Cavalieri EL. Formation of dopamine quinone-DNA adducts and their potential role in the etiology of Parkinson's disease. IUBMB Life. 2011;63(12):1087–93. doi:10.1002/iub.538.

    PubMed  CAS  Google Scholar 

  52. Sulzer D, Zecca L. Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res. 1999;1(3):181–95. doi:10.1007/bf03033289.

    Google Scholar 

  53. Sulzer D, Bogulavsky J, Larsen KE, Behr G, Karatekin E, Kleinman MH, et al. Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci U S A. 2000;97(22):11869–74. doi:10.1073/pnas.97.22.11869.

    PubMed  CAS  Google Scholar 

  54. Hastings TG, Lewis DA, Zigmond MJ. Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections. Proc Natl Acad Sci U S A. 1996;93(5):1956–61. doi:10.1073/pnas.93.5.1956.

    PubMed  CAS  Google Scholar 

  55. Benshachar D, Zuk R, Glinka Y. Dopamine neurotoxicity - inhibition of mitochondrial respiration. J Neurochem. 1995;64(2):718–23.

    CAS  Google Scholar 

  56. Asanuma M, Miyazaki I, Ogawa N. Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease. Neurotox Res. 2003;5(3):165–76.

    PubMed  Google Scholar 

  57. Chen L, Ding Y, Cagniard B, Van Laar AD, Mortimer A, Chi W, et al. Unregulated cytosolic dopamine causes neurodegeneration associated with oxidative stress in mice. J Neurosci. 2008;28(2):425–33. doi:10.1523/JNEUROSCI.3602-07.2008.

    PubMed  Google Scholar 

  58. Mosharov EV, Larsen KE, Kanter E, Phillips KA, Wilson K, Schmitz Y, et al. Interplay between cytosolic dopamine, calcium, and α-Synuclein causes selective death of substantia nigra neurons. Neuron. 2009;62(2):218–29. doi:10.1016/j.neuron.2009.01.033.

    PubMed  CAS  Google Scholar 

  59. Takahashi N, Miner LL, Sora I, Ujike H, Revay RS, Kostic V, et al. VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. Proc Natl Acad Sci U S A. 1997;94(18):9938–43.

    PubMed  CAS  Google Scholar 

  60. Wang YM, Gainetdinov RR, Fumagalli F, Xu F, Jones SR, Bock CB, et al. Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to cocaine and amphetamine. Neuron. 1997;19(6):1285–96.

    PubMed  CAS  Google Scholar 

  61. Gainetdinov RR, Fumagalli F, Wang YM, Jones SR, Levey AI, Miller GW, et al. Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice. J Neurochem. 1998;70(5):1973–8.

    PubMed  CAS  Google Scholar 

  62. Colebrooke RE, Humby T, Lynch PJ, McGowan DP, Xia J, Emson PC. Age-related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease. Eur J Neurosci. 2006;24(9):2622–30.

    PubMed  Google Scholar 

  63. Caudle WM, Richardson JR, Wang MZ, Taylor TN, Guillot TS, McCormack AL, et al. Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci. 2007;27(30):8138–48. doi:10.1523/JNEUROSCI.0319-07.2007.

    PubMed  CAS  Google Scholar 

  64. Taylor TN, Caudle WM, Shepherd KR, Noorian A, Jackson CR, Iuvone PM, et al. Nonmotor symptoms of Parkinson's Disease revealed in an animal model with reduced monoamine storage capacity. J Neurosci. 2009;29(25):8103–13. doi:10.1523/jneurosci.1495-09.2009.

    PubMed  CAS  Google Scholar 

  65. • Ulusoy A, Björklund T, Buck K, Kirik D. Dysregulated dopamine storage increases the vulnerability to α-synuclein in nigral neurons. Neurobiol Dis. 2012;47(3):367–77. Utilized lentiviralα-synuclein delivery to demonstrate synergistic toxicity of α-synuclein and cytosolic dopamine in VMAT2 hypomorphic mice.

    PubMed  CAS  Google Scholar 

  66. Guillot TS, Richardson JR, Wang MZ, Li YJ, Taylor TN, Ciliax BJ, et al. PACAP38 increases vesicular monoamine transporter 2 (VMAT2) expression and attenuates methamphetamine toxicity. Neuropeptides. 2008;42(4):423–34. doi:10.1016/j.npep.2008.04.003.

    PubMed  CAS  Google Scholar 

  67. Guillot T, Miller G. Protective actions of the vesicular monoamine transporter 2 (VMAT2) in monoaminergic neurons. Mol Neurobiol. 2009;39(2):149–70. doi:10.1007/s12035-009-8059-y.

    PubMed  CAS  Google Scholar 

  68. Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219(4587):979–80.

    PubMed  CAS  Google Scholar 

  69. Glover V, Gibb C, Sandler M. Monoamine oxidase B(MAO-B) is the major catalyst for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) oxidation in human brain and other tissues. Neurosci Lett. 1986;64(2):216–20.

    PubMed  CAS  Google Scholar 

  70. Javitch JA, D'Amato RJ, Strittmatter SM, Snyder SH. Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci U S A. 1985;82(7):2173–7.

    PubMed  CAS  Google Scholar 

  71. Langston JW, Irwin I, Langston EB, Forno LS. 1-Methyl-4-phenylpyridinium ion (MPP+): identification of a metabolite of MPTP, a toxin selective to the substantia nigra. Neurosci Lett. 1984;48(1):87–92.

    PubMed  CAS  Google Scholar 

  72. Ransom BR, Kunis DM, Irwin I, Langston JW. Astrocytes convert the parkinsonism inducing neurotoxin, MPTP, to its active metabolite, MPP+. Neurosci Lett. 1987;75(3):323–8.

    PubMed  CAS  Google Scholar 

  73. Liu Y, Peter D, Roghani A, Schuldiner S, Prive GG, Eisenberg D, et al. A cDNA that suppresses MPP + toxicity encodes a vesicular amine transporter. Cell. 1992;70(4):539–51.

    PubMed  CAS  Google Scholar 

  74. Erickson JD, Eiden LE. Functional identification and molecular cloning of a human brain vesicle monoamine transporter. J Neurochem. 1993;61(6):2314–7.

    PubMed  CAS  Google Scholar 

  75. Erickson JD, Eiden LE, Hoffman BJ. Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc Natl Acad Sci U S A. 1992;89(22):10993–7.

    PubMed  CAS  Google Scholar 

  76. Miller GW, Erickson JD, Perez JT, Penland SN, Mash DC, Rye DB, et al. Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in Parkinson's disease. Exp Neurol. 1999;156(1):138–48. doi:10.1006/exnr.1998.7008.

    PubMed  CAS  Google Scholar 

  77. Smith Y, et al. Parkinson’s disease therapeutics: new developments and challenges since the introduction of levodopa. Neuropsychopharmacology. 2012;37(1):213–46. doi:10.1038/npp.2011.212.

  78. Bertler A, Carlsson A, Nilsson J, Rosengren E. Effect of reserpine on the metabolism of catecholamies. Acta Physiologica Scand. 1957;42:22–3.

    Google Scholar 

  79. Burn JH, Rand MJ. The action of sympathomimetic amines in animals treated with reserpine. J Physiol. 1958;144(2):314–36.

    PubMed  CAS  Google Scholar 

  80. Melega WP, Williams AE, Schmitz DA, DiStefano EW, Cho AK. Pharmacokinetic and pharmacodynamic analysis of the actions of D-amphetamine and D-methamphetamine on the dopamine terminal. J Pharmacol Exp Ther. 1995;274(1):90–6.

    PubMed  CAS  Google Scholar 

  81. Sulzer D. How addictive drugs disrupt presynaptic dopamine neurotransmission. Neuron. 2011;69(4):628–49.

    PubMed  CAS  Google Scholar 

  82. Wagner GC, Ricaurte GA, Seiden LS, Schuster CR, Miller RJ, Westley J. Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine. Brain Res. 1980;181(1):151–60. doi:10.1016/0006-8993(80)91265-2.

    PubMed  CAS  Google Scholar 

  83. Larsen KE, Fon EA, Hastings TG, Edwards RH, Sulzer D. Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis. J Neurosci. 2002;22(20):8951–60.

    PubMed  CAS  Google Scholar 

  84. Yamamoto BK, Moszczynska A, Gudelsky GA. Amphetamine toxicities. Ann NY Acad Sci. 2010;1187(1):101–21. doi:10.1111/j.1749-6632.2009.05141.x.

    PubMed  CAS  Google Scholar 

  85. LaVoie MJ, Hastings TG. Dopamine quinone formation and protein modification associated with the striatal neurotoxicity of methamphetamine: evidence against a role for extracellular dopamine. J Neurosci. 1999;19(4):1484–91.

    PubMed  CAS  Google Scholar 

  86. Villemagne V, Yuan J, Wong DF, Dannals RF, Hatzidimitriou G, Mathews WB, et al. Brain dopamine neurotoxicity in baboons treated with doses of methamphetamine comparable with those recreationally abused by humans: evidence from C-11 WIN-35,428 positron emission tomography studies and direct in vitro determinations. J Neurosci. 1998;18(1):419–27.

    PubMed  CAS  Google Scholar 

  87. McCann UD, Wong DF, Yokoi F, Villemagne V, Dannals RF, Ricaurte GA. Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: evidence from positron emission tomography studies with C-11 WIN-35,428. J Neurosci. 1998;18(20):8417–22.

    PubMed  CAS  Google Scholar 

  88. Callaghan RC, Cunningham JK, Sykes J, Kish SJ. Increased risk of Parkinson's disease in individuals hospitalized with conditions related to the use of methamphetamine or other amphetamine-type drugs. Drug Alcohol Depend. 2012;120(1–3):35–40. doi:10.1016/j.drugalcdep.2011.06.013.

    PubMed  CAS  Google Scholar 

  89. Guillot TS, Shepherd KR, Richardson JR, Wang MZ, Li YJ, Emson PC, et al. Reduced vesicular storage of dopamine exacerbates methamphetamine-induced neurodegeneration and astrogliosis. J Neurochem. 2008;106(5):2205–17. doi:10.1111/j.1471-4159.2008.05568.x.

    PubMed  CAS  Google Scholar 

  90. Ascherio A, Chen H, Weisskopf MG, O'Reilly E, McCullough ML, Calle EE, et al. Pesticide exposure and risk for Parkinson's disease. Ann Neurol. 2006;60:197–203. doi:10.1002/ana.20904.

    PubMed  CAS  Google Scholar 

  91. Elbaz A, Clavel J, Rathouz PJ, Moisan F, Galanaud J-P, Delemotte B, et al. Professional exposure to pesticides and Parkinson disease. Ann Neurol. 2009;66:494–504. doi:10.1002/ana.21717.

    PubMed  Google Scholar 

  92. Priyadarshi A, Khuder SA, Schaub EA, Priyadarshi SS. Environmental risk factors and Parkinson's disease: a meta-analysis. Environ Res. 2001;86:122–7. doi:10.1006/enrs.2001.4264.

    PubMed  CAS  Google Scholar 

  93. Priyadarshi A, Khuder SA, Schaub EA, Shrivastava S. A meta-analysis of Parkinson's disease and exposure to pesticides. Neurotoxicology. 2000;21:435–40.

    PubMed  CAS  Google Scholar 

  94. Semchuk KM, Love EJ, Lee RG. Parkinson's disease and exposure to rural environmental factors: a population based case-control study. Can J Neurol Sci. 1991;18:279–86.

    PubMed  CAS  Google Scholar 

  95. Semchuk KM, Love EJ, Lee RG. Parkinson's disease and exposure to agricultural work and pesticide chemicals. Neurology. 1992;42:1328–35.

    PubMed  CAS  Google Scholar 

  96. Steenland K, Hein MJ, Cassinelli RT, Prince MM, Nilsen NB, Whelan EA, et al. Polychlorinated biphenyls and neurodegenerative disease mortality in an occupational cohort. Epidemiology. 2006;17:8–13. doi:10.1097/01.ede.0000190707.51536.2b.

    PubMed  Google Scholar 

  97. Tanner CM. Parkinson's disease: environmental etiologic factors. Curr Opin Neurol. 1990;3.

  98. Ritz B, Costello S. Geographic model and biomarker-derived measures of pesticide exposure and Parkinson's disease. Ann N Y Acad Sci. 2006;1076:378–87. doi:10.1196/annals.1371.074.

    PubMed  CAS  Google Scholar 

  99. Gatto NM, Cockburn M, Bronstein J, Manthripragada AD, Ritz B. Well-water consumption and Parkinson's disease in rural California. Environ Health Perspect. 2009;117(12):1912–8. doi:10.1289/ehp.0900852.

    PubMed  CAS  Google Scholar 

  100. Caudle WM, Guillot TS, Lazo CR, Miller GW. Industrial toxicants and Parkinson's disease. Neurotoxicology. 2012;33:178–88. doi:10.1016/j.neuro.2012.01.010.

    PubMed  CAS  Google Scholar 

  101. Hatcher JM, Miller GW, Pennell KD. Parkinson's disease and pesticides: a toxicological perspective. Trends Pharmacol Sci. 2008;29:322–9. doi:10.1016/j.tips.2008.03.007.

    PubMed  CAS  Google Scholar 

  102. Corrigan F, Wienburg C, Daniel S, Mann D. Organochlorine insecticides in substantia nigra in Parkinson’s disease. J Toxicol Environ Health Part A. 2000;59:229–34.

    PubMed  CAS  Google Scholar 

  103. Corrigan FM, Murray L, Wyatt CL, Shore RF. Diorthosubstituted polychlorinated biphenyls in caudate nucleus in Parkinson's disease. Exp Neurol. 1998;150:339–42. doi:10.1006/exnr.1998.6776.

    PubMed  CAS  Google Scholar 

  104. Fleming L, Mann JB, Bean J, Briggle T, Sanchez-Ramos JR. Parkinson's disease and brain levels of organochlorine pesticides. Ann Neurol. 1994;36:100–3. doi:10.1002/ana.410360119.

    PubMed  CAS  Google Scholar 

  105. Hatcher-Martin JM, Gearing M, Steenland K, Levey AI, Miller GW, Pennell KD. Association between polychlorinated biphenyls and Parkinson's disease neuropathology. Neurotoxicology. 2012;33:1298–304. doi:10.1016/j.neuro.2012.08.002.

    PubMed  CAS  Google Scholar 

  106. Weisskopf MG, Knekt P, O'Reilly EJ, Lyytinen J, Reunanen A, Laden F, et al. Persistent organochlorine pesticides in serum and risk of Parkinson disease. Neurology. 2010;74:1055–61. doi:10.1212/WNL.0b013e3181d76a93.

    PubMed  CAS  Google Scholar 

  107. Miller GW, Kirby M, Levey AI, Bloomquist J. Heptachlor alters expression and function of dopamine transporters. Neurotoxicology. 1999;20:631–7.

    PubMed  CAS  Google Scholar 

  108. Bemis JC, Seegal RF. PCB-induced inhibition of the vesicular monoamine transporter predicts reductions in synaptosomal dopamine content. Toxicol Sci. 2004;80:288–95. doi:10.1093/toxsci/kfh153.

    PubMed  CAS  Google Scholar 

  109. Caudle WM, Richardson JR, Delea KC, Guillot TS, Wang M, Pennell KD, et al. Polychlorinated biphenyl-induced reduction of dopamine transporter expression as a precursor to Parkinson's disease-associated dopamine toxicity. Toxicol Sci. 2006;92:490–9. doi:10.1093/toxsci/kfl018.

    PubMed  CAS  Google Scholar 

  110. Caudle WM, Richardson JR, Wang M, Miller GW. Perinatal heptachlor exposure increases expression of presynaptic dopaminergic markers in mouse striatum. Neurotoxicology. 2005;26:721–8. doi:10.1016/j.neuro.2004.09.003.

    PubMed  CAS  Google Scholar 

  111. Fonnum F, Mariussen E, Reistad T. Molecular mechanisms involved in the toxic effects of polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs). J Toxicol Environ Health Part A. 2006;69(1–2):21–35. doi:10.1080/15287390500259020.

    PubMed  CAS  Google Scholar 

  112. Hatcher JM, Di Monte DA, Richardson JR, Guillot TS, McCormack AL, Jones DP, et al. Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system. Exp Neurol. 2007;204:619–30. doi:10.1016/j.expneurol.2006.12.020.

    PubMed  CAS  Google Scholar 

  113. Kitazawa M, Anantharam V, Kanthasamy A. Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptotic cell death in dopaminergic cells. Free Radical Biol Med. 2001;31:1473–85.

    CAS  Google Scholar 

  114. Lee DW, Opanashuk LA. Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in dopaminergic cell injury. Neurotoxicology. 2004;25:925–39. doi:10.1016/j.neuro.2004.05.005.

    PubMed  CAS  Google Scholar 

  115. Richardson JR, Caudle WM, Wang M, Dean ED, Pennell KD, Miller GW. Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson's disease. FASEB J. 2006;20:1695–7. doi:10.1096/fj.06-5864fje.

    PubMed  CAS  Google Scholar 

  116. Richardson JR, Miller GW. Acute exposure to aroclor 1016 or 1260 differentially affects dopamine transporter and vesicular monoamine transporter 2 levels. Toxicol Lett. 2004;148:29–40.

    PubMed  CAS  Google Scholar 

  117. Sanchez-Ramos J, Facca A, Basit A, Song S. Toxicity of dieldrin for dopaminergic neurons in mesencephalic cultures. Exp Neurol. 1998;150:263–71. doi:10.1006/exnr.1997.6770.

    PubMed  CAS  Google Scholar 

  118. Seegal R, Brosch K, Bush B. Polychlorinated biphenyls produces regional alterations of dopamine metabolism in rat brain. Toxicol Lett. 1986;30:197–202.

    PubMed  CAS  Google Scholar 

  119. Seegal R, Bush B, Shain W. Lightly chlorinated ortho-substituted PCB congeners decrease dopamine in nonhuman primate brain and in tissue culture. Toxicol Appl Pharmacol. 1990;106:136–44.

    PubMed  CAS  Google Scholar 

  120. Seegal RF. The neurotoxicological consequences of developmental exposure to PCBs. Toxicol Sci. 2000;57:1–3.

    PubMed  CAS  Google Scholar 

  121. Seegal RF, Okoniewski R, Brosch K, Bemis JC. Polychlorinated biphenyls alter extraneuronal but not tissue dopamine concentrations in adult rat striatum: an in vivo microdialysis study. Environ Health Perspect. 2002;110:1113–7.

    PubMed  CAS  Google Scholar 

  122. Bradner JM, Suragh TA, Wilson WW, Lazo CR, Stout KA, Kim HM, et al. Exposure to the polybrominated diphenyl ether mixture DE-71 damages the nigrostriatal dopamine system: role of dopamine handling in neurotoxicity. Exp Neurol. 2013;241:138–47. doi:10.1016/j.expneurol.2012.12.013.

    PubMed  CAS  Google Scholar 

  123. Mariussen E, Morch Andersen J, Fonnum F. The effect of polychlorinated biphenyls on the uptake of dopamine and other neurotransmitters into rat brain synaptic vesicles. Toxicol Appl Pharmaco. 1999;161(3):274–82 doi:10.1006/taap.1999.8806.

    Google Scholar 

  124. Mariussen E, Fonnum F. The effect of brominated flame retardants on neurotransmitter uptake into rat brain synaptosomes and vesicles. Neurochem Int. 2003;43(4–5):533–42.

    Google Scholar 

  125. Mariussen E. Neurotoxic effects of perfluoroalkylated compounds: mechanisms of action and environmental relevance. Arch Toxicol. 2012;86(9):1349–67. doi:10.1007/s00204-012-0822-6.

    Google Scholar 

  126. • Rilstone JJ, Alkhater RA, Minassian BA. Brain dopamine-serotonin vesicular transport disease and its treatment. N Engl J Med. 2013. A case report highlighting a recessive mutation in a coding region of the VMAT2 gene causing infantile-onset parkinsonism in a consanguineous pedigree.

  127. Glatt CE, DeYoung JA, Delgado S, Service SK, Giacomini KM, Edwards RH, et al. Screening a large reference sample to identify very low frequency sequence variants: comparisons between 2 genes. Nat Genet. 2001;27(4):435–8. doi:10.1038/86948.

    PubMed  CAS  Google Scholar 

  128. Burman J, Tran CH, Glatt C, Freimer NB, Edwards RH. The effect of rare human sequence variants on the function of vesicular monoamine transporter 2. Pharmacogenetics. 2004;14(9):587–94. doi:10.1097/00008571-200409000-00003.

    PubMed  CAS  Google Scholar 

  129. Lin ZC, Zhao Y, Chung CY, Zhou YH, Xiong NA, Glatt CE, et al. High regulatability favors genetic selection in SLC18A2, a vesicular monoamine transporter essential for life. FASEB J. 2010;24(7):2191–200. doi:10.1096/fj.09-140368.

    PubMed  CAS  Google Scholar 

  130. Lill CM, Roehr JT, McQueen MB, Kavvoura FK, Bagade S, Schjeide BM, et al. Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: the PDGene database. PLoS Genetics. 2012;8(3):e1002548. doi:10.1371/journal.pgen.1002548.

    PubMed  CAS  Google Scholar 

  131. Glatt CE, Wahner AD, White DJ, Ruiz-Linares A, Ritz B. Gain-of-function haplotypes in the vesicular monoamine transporter promoter are protective for Parkinson disease in women. Hum Mol Genet. 2006;15(2):299–305. doi:10.1093/hmg/ddi445.

    PubMed  CAS  Google Scholar 

  132. • Brighina L, Riva C, Bertola F, Saracchi E, Fermi S, Goldwurm S, et al. Analysis of vesicular monoamine transporter 2 polymorphisms in Parkinson's disease. Neurobiol Aging. 2013. doi:10.1016/j.neurobiolaging.2012.12.020. Identified 2 SNPs in the VMAT2 promoter that are associated with risk of PD.

    PubMed  Google Scholar 

  133. Bohnen NI, Albin RL, Koeppe RA, Wernette KA, Kilbourn MR, Minoshima S, et al. Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease. J Cerebral Blood Flow Metab. 2006;26(9):1198–212. doi:10.1038/sj.jcbfm.9600276.

    CAS  Google Scholar 

  134. Frey KA, Koeppe RA, Kilbourn MR, VanderBorght TM, Albin RL, Gilman S, et al. Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging. Ann Neurol. 1996;40(6):873–84. doi:10.1002/ana.410400609.

    PubMed  CAS  Google Scholar 

  135. Albin RL, Nichols TE, Frey KA. Brain imaging to assess the effects of dopamine agonists on progression of Parkinson disease. JAMA. 2002;288(3):311–2. author reply 2–3.

    PubMed  Google Scholar 

  136. Hauser RA, Koller WC, Hubble JP, Malapira T, Busenbark K, Olanow CW. Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson' s disease. Mov Disord. 2000;15(3):485–9.

    PubMed  CAS  Google Scholar 

  137. Kish SJ, Zhong XH, Hornykiewicz O, Haycock JW. Striatal 3,4-dihydroxyphenylalanine decarboxylase in aging: disparity between postmortem and positron emission tomography studies? Ann Neurol. 1995;38(2):260–4. doi:10.1002/ana.410380220.

    PubMed  CAS  Google Scholar 

  138. Tedroff J, Ekesbo A, Rydin E, Langstrom B, Hagberg G. Regulation of dopaminergic activity in early Parkinson's disease. Ann Neurol. 1999;46(3):359–65.

    PubMed  CAS  Google Scholar 

  139. Damier P, Hirsch EC, Agid Y, Graybiel AM. The substantia nigra of the human brain: II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain. 1999;122(8):1437–48. doi:10.1093/brain/122.8.1437.

    PubMed  Google Scholar 

  140. Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, et al. In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease. Ann Neurol. 2000;47(4):493–503. doi:10.1002/1531-8249(200004)47:4<493::aid-ana13>3.0.co;2-4.

    PubMed  CAS  Google Scholar 

  141. Kilbourn MR, Frey KA, Vander Borght T, Sherman PS. Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters. Nucl Med Biol. 1996;23(4):467–71.

    PubMed  CAS  Google Scholar 

  142. Okamura N, Villemagne VL, Drago J, Pejoska S, Dhamija RK, Mulligan RS, et al. In vivo Measurement of vesicular monoamine transporter type 2 density in Parkinson Disease with F-18-AV-133. J Nucl Med. 2010;51(2):223–8. doi:10.2967/jnumed.109.070094.

    PubMed  Google Scholar 

  143. Chao KT, Tsao HH, Weng YH, Hsiao IT, Hsieh CJ, Wey SP, et al. Quantitative analysis of binding sites for 9-fluoropropyl-(+)-dihydrotetrabenazine (18F AV-133) in a MPTP-lesioned PD mouse model. Synapse. 2012;66(9):823–31. doi:10.1002/syn.21572.

    PubMed  CAS  Google Scholar 

  144. Velseboer DC, de Haan RJ, Wieling W, Goldstein DS, de Bie RM. Prevalence of orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2011;17(10):724–9. doi:10.1016/j.parkreldis.2011.04.016.

    PubMed  Google Scholar 

  145. Jain S, Goldstein DS. Cardiovascular dysautonomia in Parkinson disease: from pathophysiology to pathogenesis. Neurobiol Dis. 2012;46(3):572–80. doi:10.1016/j.nbd.2011.10.025.

    PubMed  CAS  Google Scholar 

  146. Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H. I-123-metaiodobenzylguanidine myocardial scintigraphy in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1999;67(2):189–94. doi:10.1136/jnnp.67.2.189.

    PubMed  CAS  Google Scholar 

  147. Li S-T, Dendi R, Holmes C, Goldstein DS. Progressive loss of cardiac sympathetic innervation in Parkinson's disease. Ann Neurol. 2002;52(2):220–3. doi:10.1002/ana.10236.

    PubMed  Google Scholar 

  148. Orimo S, Suzuki M, Inaba A, Mizusawa H. 123I-MIBG myocardial scintigraphy for differentiating Parkinson’s disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2012;18(5):494–500. doi:10.1016/j.parkreldis.2012.01.009.

    PubMed  Google Scholar 

  149. Tijero B, Gomez-Esteban JC, Llorens V, Lezcano E, Gonzalez-Fernandez MC, de Pancorbo MM, et al. Cardiac sympathetic denervation precedes nigrostriatal loss in the E46K mutation of the alpha-synuclein gene (SNCA). Clin Autonomic Res. 2010;20(4):267–9. doi:10.1007/s10286-010-0068-4.

    CAS  Google Scholar 

  150. Wong KK, Raffel DM, Koeppe RA, Frey KA, Bohnen NI, Gilman S. Pattern of cardiac sympathetic denervation in idiopathic Parkinson Disease studied with 11C Hydroxyephedrine PET. Radiology. 2012. doi:10.1148/radiol.12112723.

    Google Scholar 

  151. Goldstein DS, Holmes C, Sewell L, Park MY, Sharabi Y. Sympathetic noradrenergic before striatal dopaminergic denervation: relevance to Braak staging of synucleinopathy. Clin Autonomic Res. 2012;22(1):57–61. doi:10.1007/s10286-011-0136-4.

    Google Scholar 

  152. Goldstein DS, Holmes C, Kopin IJ, Sharabi Y. Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases. J Clin Invest. 2011;121(8):3320–30. doi:10.1172/JCI.45803.

    PubMed  CAS  Google Scholar 

  153. Eisenhofer G, Hovevey-Sion D, Kopin IJ, Miletich R, Kirk KL, Finn R, et al. Neuronal uptake and metabolism of 2- and 6-fluorodopamine: false neurotransmitters for positron emission tomographic imaging of sympathetically innervated tissues. J Pharmacol ExpTherapeut. 1989;248(1):419–27.

    CAS  Google Scholar 

  154. Lotharius J, Brundin P. Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Hum Mol Genet. 2002;11(20):2395–407. doi:10.1093/hmg/11.20.2395.

    PubMed  CAS  Google Scholar 

  155. Pletscher A. Platelets as models: use and limitations. Experientia. 1988;44(2):152–5. doi:10.1007/bf01952200.

    PubMed  CAS  Google Scholar 

  156. Paul SM, Rehavi M, Skolnick P, Ballenger JC, Goodwin FK. Depressed patients have decreased binding of tritiated imipramine to platelet serotonin transporter. Arch Gen Psychiatry. 1981;38(12):1315–7.

    PubMed  CAS  Google Scholar 

  157. Weizman R, Carmi M, Tyano S, Rehavi M. Reduced 3H-imipramine binding but unaltered 3H-serotonin uptake in platelets of adolescent enuretics. Psychiatry Res. 1986;19(1):37–42.

    PubMed  CAS  Google Scholar 

  158. Weizman R, Carmi M, Tyano S, Apter A, Rehavi M. High affinity [3H]imipramine binding and serotonin uptake to platelets of adolescent females suffering from anorexia nervosa. Life Sci. 1986;38(13):1235–42.

    PubMed  CAS  Google Scholar 

  159. Weizman A, Carmi M, Hermesh H, Shahar A, Apter A, Tyano S, et al. High-affinity imipramine binding and serotonin uptake in platelets of eight adolescent and ten adult obsessive-compulsive patients. Am J Psychiatry. 1986;143(3):335–9.

    PubMed  CAS  Google Scholar 

  160. Yubero-Lahoz S, Robledo P, Farre M, de la Torre R. Platelet SERT as a peripheral biomarker of serotonergic neurotransmission in the central nervous system. Curr Med Chem. 2013.

  161. Zalsman G, Aslanov-Farbstein D, Rehavi M, Roz N, Vermeiren R, Laor N, et al. Platelet vesicular monoamine transporter 2 density in the disruptive behavior disorders. J Child Adolesc Psychopharmacol. 2011;21(4):341–4. doi:10.1089/cap.2010.0148.

    PubMed  Google Scholar 

  162. Zalsman G, Rehavi M, Roz N, Laor N, Weizman A, Toren P. Altered affinity of the platelet vesicular monoamine transporter 2 to dihydrotetrabenazine in children with major depression. J Neural Transm. 2011;118(9):1383–7. doi:10.1007/s00702-011-0643-4.

    PubMed  Google Scholar 

  163. Schwartz K, Iancu I, Stryjer R, Chelben J, Kotler M, Weizman A, et al. Reduced platelet vesicular monoamine transporter density in smoking schizophrenia patients. Eur Neuropsychopharmacol. 2005;15(5):557–61. doi:10.1016/j.euroneuro.2005.02.005.

    PubMed  CAS  Google Scholar 

  164. Schwartz K, Weizman A, Rehavi M. Decreased platelet vesicular monoamine transporter density in habitual smokers. Eur Neuropsychopharmacol. 2005;15(2):235–8. doi:10.1016/j.euroneuro.2004.11.001.

    PubMed  CAS  Google Scholar 

  165. Toren P, Rehavi M, Luski A, Roz N, Laor N, Lask M, et al. Decreased platelet vesicular monoamine transporter density in children and adolescents with attention deficit/hyperactivity disorder. Eur Neuropsychopharmacol. 2005;15(2):159–62. doi:10.1016/j.euroneuro.2004.07.002.

    PubMed  CAS  Google Scholar 

  166. Zucker M, Aviv A, Shelef A, Weizman A, Rehavi M. Elevated platelet vesicular monoamine transporter density in untreated patients diagnosed with major depression. Psychiatry Res. 2002;112(3):251–6.

    PubMed  CAS  Google Scholar 

  167. Zucker M, Valevski A, Weizman A, Rehavi M. Increased platelet vesicular monoamine transporter density in adult schizophrenia patients. Eur Neuropsychopharmacol. 2002;12(4):343–7.

    PubMed  CAS  Google Scholar 

  168. Zucker M, Weizman A, Harel D, Rehavi M. Changes in vesicular monoamine transporter (VMAT2) and synaptophysin in rat Substantia nigra and prefrontal cortex induced by psychotropic drugs. Neuropsychobiology. 2001;44(4):187–91.

    PubMed  CAS  Google Scholar 

  169. Zucker M, Weizman A, Rehavi M. Characterization of high-affinity [3H]TBZOH binding to the human platelet vesicular monoamine transporter. Life Sci. 2001;69(19):2311–7.

    PubMed  CAS  Google Scholar 

  170. Sala G, Brighina L, Saracchi E, Fermi S, Riva C, Carrozza V, et al. Vesicular monoamine transporter 2 mRNA levels are reduced in platelets from patients with Parkinson's disease. J Neural Transm. 2010;117(9):1093–8. doi:10.1007/s00702-010-0446-z.

    PubMed  CAS  Google Scholar 

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Acknowledgments

P01 ES016731, T32 ES012870, T32 GM008602, and T32 DA015040.

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Shawn P. Alter declares that he has no conflict of interest.

Gina M. Lenzi declares that she has no conflict of interest.

Alison I. Bernstein declares that she has no conflict of interest.

Gary W. Miller declares that he has no conflict of interest.

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Authors and Affiliations

  1. Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Shawn P. Alter & Alison I. Bernstein

  2. Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA

    Gina M. Lenzi

  3. Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA

    Gary W. Miller

  4. Department of Pharmacology, School of Medicine, Emory University, Atlanta, GA, USA

    Gary W. Miller

  5. Department of Environmental Health, Rollins School of Public Health, Claudia Nance Rollins Bldg, Room 8007, 1518 Clifton Road, NE, Atlanta, GA, 30322, USA

    Gary W. Miller

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  1. Shawn P. Alter
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Correspondence to Gary W. Miller.

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This article is part of the Topical Collection on Movement Disorders

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Alter, S.P., Lenzi, G.M., Bernstein, A.I. et al. Vesicular Integrity in Parkinson’s Disease. Curr Neurol Neurosci Rep 13, 362 (2013). https://doi.org/10.1007/s11910-013-0362-3

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