Molecular Neurobiology

, Volume 55, Issue 5, pp 4240–4252 | Cite as

Effect of Intrastriatal 6-OHDA Lesions on Extrastriatal Brain Structures in the Mouse

  • Birte Becker
  • Melek Demirbas
  • Sonja Johann
  • Adib Zendedel
  • Cordian Beyer
  • Hans Clusmann
  • Stefan Jean-Pierre Haas
  • Andreas Wree
  • Sonny Kian Hwie Tan
  • Markus Kipp
Article

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of midbrain dopaminergic neurons, resulting in motor and non-motor symptoms. The underlying pathology of non-motor symptoms is poorly understood. Discussed are pathological changes of extrastriatal brain structures. In this study, we characterized histopathological alterations of extrastriatal brain structures in the 6-hydroxydopamine (6-OHDA) PD animal model. Lesions were induced by unilateral stereotactic injections of 6-OHDA into the striatum or medial forebrain bundle of adult male mice. Loss of tyrosine hydroxylase positive (TH+) fibers as well as glia activation was quantified following stereological principles. Loss of dopaminergic innervation was further investigated by western-blotting. As expected, 6-OHDA injection into the nigrostriatal route induced retrograde degeneration of dopaminergic neurons within the substantia nigra pars compacta (SNpc), less so within the ventral tegmental area. Furthermore, we observed a region-specific drop of TH+ projection fiber density in distinct cortical regions. This pathology was most pronounced in the cingulate- and motor cortex, whereas the piriform cortex was just modestly affected. Loss of cortical TH+ fibers was not paralleled by microglia or astrocyte activation. Our results demonstrate that the loss of dopaminergic neurons within the substantia nigra pars compacta is paralleled by a cortical dopaminergic denervation in the 6-OHDA model. This model serves as a valuable tool to investigate mechanisms operant during cortical pathology in PD patients. Further studies are needed to understand why cortical dopaminergic innervation is lost in this model, and what functional consequence is associated with the observed denervation.

Keywords

Parkinson’s disease 6-OHDA Nigrostriatal lesion Mouse Tyrosine hydroxylase Cerebral cortex 

Notes

Acknowledgements

This study was supported by IZKF grants from the Faculty of Medicine (MK and ST). We thank Petra Ibold and Helga Helten for their valuable technical assistance.

Compliance with Ethical Standards

All procedures were conducted in accordance with local regulations and have been approved by the local Animal Commission (Iran and Rostock/Germany).

References

  1. 1.
    World Health Organization W (2006) Neurological disorders: public health challenges. World Health OrganizationGoogle Scholar
  2. 2.
    Farrer MJ (2006) Genetics of Parkinson disease: paradigm shifts and future prospects. Nat Rev Genet 7(4):306–318. doi: 10.1038/nrg1831 CrossRefPubMedGoogle Scholar
  3. 3.
    Chaudhuri KR, Schapira AHV (2009) Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 8(5):464–474. doi: 10.1016/S1474-4422(09)70068-7 CrossRefPubMedGoogle Scholar
  4. 4.
    Bezard E, Yue Z, Kirik D, Spillantini MG (2013) Animal models of Parkinson’s disease: limits and relevance to neuroprotection studies. Mov Disord 28(1):61–70. doi: 10.1002/mds.25108 CrossRefPubMedGoogle Scholar
  5. 5.
    Blandini F, Levandis G, Bazzini E, Nappi G, Armentero M-T (2007) Time-course of nigrostriatal damage, basal ganglia metabolic changes and behavioural alterations following intrastriatal injection of 6-hydroxydopamine in the rat: new clues from an old model. Eur J Neurosci 25(2):397–405. doi: 10.1111/j.1460-9568.2006.05285.x CrossRefPubMedGoogle Scholar
  6. 6.
    Przedborski S, Levivier M, Jiang H, Ferreira M, Jackson-Lewis V, Donaldson D, Togasaki DM (1995) Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine. Neuroscience 67(3):631–647CrossRefPubMedGoogle Scholar
  7. 7.
    Sauer H, Oertel WH (1994) Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat. Neuroscience 59(2):401–415. doi: 10.1016/0306-4522(94)90605-X CrossRefPubMedGoogle Scholar
  8. 8.
    Stott SR, Barker RA (2014) Time course of dopamine neuron loss and glial response in the 6-OHDA striatal mouse model of Parkinson’s disease. Eur J Neurosci 39(6):1042–1056. doi: 10.1111/ejn.12459 CrossRefPubMedGoogle Scholar
  9. 9.
    Gravotta L, Gavrila AM, Hood S, Amir S (2011) Global depletion of dopamine using intracerebroventricular 6-hydroxydopamine injection disrupts normal circadian wheel-running patterns and PERIOD2 expression in the rat forebrain. J Mol Neurosci 45(2):162–171. doi: 10.1007/s12031-011-9520-8 CrossRefPubMedGoogle Scholar
  10. 10.
    Requejo C, Ruiz-Ortega JA, Bengoetxea H, Garcia-Blanco A, Herran E, Aristieta A, Igartua M, Pedraz JL et al (2016) Morphological changes in a severe model of Parkinson’s disease and its suitability to test the therapeutic effects of microencapsulated neurotrophic factors. Mol Neurobiol. doi: 10.1007/s12035-016-0244-1
  11. 11.
    Berger B, Tassin JP, Blanc G, Moyne MA, Thierry AM (1974) Histochemical confirmation for dopaminergic innervation of the rat cerebral cortex after destruction of the noradrenergic ascending pathways. Brain Res 81(2):332–337. doi: 10.1016/0006-8993(74)90948-2 CrossRefPubMedGoogle Scholar
  12. 12.
    Fallon JH, Moore RY (1978) Catecholamine innervation of the basal forebrain. III. Olfactory bulb, anterior olfactory nuclei, olfactory tubercle and piriform cortex. J Comp Neurol 180(3):533–544. doi: 10.1002/cne.901800309 CrossRefPubMedGoogle Scholar
  13. 13.
    Gaspar P, Berger B, Febvret A, Vigny A, Henry JP (1989) Catecholamine innervation of the human cerebral cortex as revealed by comparative immunohistochemistry of tyrosine hydroxylase and dopamine-beta-hydroxylase. J Comp Neurol 279(2):249–271. doi: 10.1002/cne.902790208 CrossRefPubMedGoogle Scholar
  14. 14.
    Verney C, Baulac M, Berger B, Alvarez C, Vigny A, Helle KB (1985) Morphological evidence for a dopaminergic terminal field in the hippocampal formation of young and adult rat. Neuroscience 14(4):1039–1052. doi: 10.1016/0306-4522(85)90275-1 CrossRefPubMedGoogle Scholar
  15. 15.
    Baulac M, Verney C, Berger B (1986) Dopaminergic innervation of the parahippocampal and hippocampal regions in the rat. Rev Neurol 142(12):895–905PubMedGoogle Scholar
  16. 16.
    Gasbarri A, Verney C, Innocenzi R, Campana E, Pacitti C (1994) Mesolimbic dopaminergic neurons innervating the hippocampal formation in the rat: a combined retrograde tracing and immunohistochemical study. Brain Res 668(1–2):71–79. doi: 10.1016/0006-8993(94)90512-6 CrossRefPubMedGoogle Scholar
  17. 17.
    Goldsmith SK, Joyce JN (1994) Dopamine D2 receptor expression in hippocampus and parahippocampal cortex of rat, cat, and human in relation to tyrosine hydroxylase-immunoreactive fibers. Hippocampus 4(3):354–373. doi: 10.1002/hipo.450040318 CrossRefPubMedGoogle Scholar
  18. 18.
    Kalia M, Fuxe K, Goldstein M (1985) Rat medulla oblongata. II. Dopaminergic, noradrenergic (A1 and A2) and adrenergic neurons, nerve fibers, and presumptive terminal processes. J Comp Neurol 233(3):308–332. doi: 10.1002/cne.902330303 CrossRefPubMedGoogle Scholar
  19. 19.
    Gaspar P, Duyckaerts C, Alvarez C, Javoy-Agid F, Berger B (1991) Alterations of dopaminergic and noradrenergic innervations in motor cortex in Parkinson’s disease. Ann Neurol 30(3):365–374. doi: 10.1002/ana.410300308 CrossRefPubMedGoogle Scholar
  20. 20.
    Tzschentke TM (2001) Pharmacology and behavioral pharmacology of the mesocortical dopamine system. Prog Neurobiol 63(3):241–320CrossRefPubMedGoogle Scholar
  21. 21.
    Paxinos G, Franklin KBJ (2001) Mouse brain in stereotaxic coordinates, 2nd edn. Academic, San DiegoGoogle Scholar
  22. 22.
    Slowik A, Schmidt T, Beyer C, Amor S, Clarner T, Kipp M (2015) The sphingosine 1-phosphate receptor agonist FTY720 is neuroprotective after cuprizone-induced CNS demyelination. Br J Pharmacol 172(1):80–92. doi: 10.1111/bph.12938 CrossRefPubMedGoogle Scholar
  23. 23.
    Dunnett SB, Iversen SD (1982) Spontaneous and drug-induced rotation following localized 6-hydroxydopamine and kainic acid-induced lesions of the neostriatum. Neuropharmacology 21(9):899–908CrossRefPubMedGoogle Scholar
  24. 24.
    Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res 24(3):485–493CrossRefPubMedGoogle Scholar
  25. 25.
    Wagenknecht N, Becker B, Scheld M, Beyer C, Clarner T, Hochstrasser T, Kipp M (2016) Thalamus degeneration and inflammation in two distinct multiple sclerosis animal models. J Mol Neurosci 60(1):102–114. doi: 10.1007/s12031-016-0790-z CrossRefPubMedGoogle Scholar
  26. 26.
    Grosse-Veldmann R, Becker B, Amor S, van der Valk P, Beyer C, Kipp M (2016) Lesion expansion in experimental demyelination animal models and multiple sclerosis lesions. Mol Neurobiol 53(7):4905–4917. doi: 10.1007/s12035-015-9420-y CrossRefPubMedGoogle Scholar
  27. 27.
    Hochstrasser T, Exner GL, Nyamoya S, Schmitz C, Kipp M (2017) Cuprizone-containing pellets are less potent to induce consistent demyelination in the corpus callosum of C57BL/6 mice. J Mol Neurosci 61(4):617–624. doi: 10.1007/s12031-017-0903-3 CrossRefPubMedGoogle Scholar
  28. 28.
    Goldberg J, Clarner T, Beyer C, Kipp M (2015) Anatomical distribution of cuprizone-induced lesions in C57BL6 mice. J Mol Neurosci 57(2):166–175. doi: 10.1007/s12031-015-0595-5 CrossRefPubMedGoogle Scholar
  29. 29.
    Mangano EN, Peters S, Litteljohn D, So R, Bethune C, Bobyn J, Clarke M, Hayley S (2011) Granulocyte macrophage-colony stimulating factor protects against substantia nigra dopaminergic cell loss in an environmental toxin model of Parkinson’s disease. Neurobiol Dis 43(1):99–112. doi: 10.1016/j.nbd.2011.02.011 CrossRefPubMedGoogle Scholar
  30. 30.
    Li HP, Komuta Y, Kimura-Kuroda J, van Kuppevelt TH, Kawano H (2013) Roles of chondroitin sulfate and dermatan sulfate in the formation of a lesion scar and axonal regeneration after traumatic injury of the mouse brain. J Neurotrauma 30(5):413–425. doi: 10.1089/neu.2012.2513 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Heppner FL, Roth K, Nitsch R, Hailer NP (1998) Vitamin E induces ramification and downregulation of adhesion molecules in cultured microglial cells. Glia 22(2):180–188CrossRefPubMedGoogle Scholar
  32. 32.
    Eder C, Schilling T, Heinemann U, Haas D, Hailer N, Nitsch R (1999) Morphological, immunophenotypical and electrophysiological properties of resting microglia in vitro. Eur J Neurosci 11(12):4251–4261CrossRefPubMedGoogle Scholar
  33. 33.
    Häggendal J, Hamberger B (1967) Quantitative in vitro studies on noradrenaline uptake and its inhibition by amphetamine, desipramine and chlorpromazine. Acta Physiol Scand 70(3–4):277–280. doi: 10.1111/j.1748-1716.1967.tb03626.x CrossRefPubMedGoogle Scholar
  34. 34.
    Ross SB, Renyi AL (1967) Inhibition of the uptake of tritiated catecholamines by antidepressant and related agents. Eur J Pharmacol 2(3):181–186CrossRefPubMedGoogle Scholar
  35. 35.
    Hudson JL, van Horne CG, Strömberg I, Brock S, Clayton J, Masserano J, Hoffer BJ, Gerhardt GA (1993) Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats. Brain Res 626(1–2):167–174CrossRefPubMedGoogle Scholar
  36. 36.
    Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res 24(3):485–493. doi: 10.1016/0006-8993(70)90187-3 CrossRefPubMedGoogle Scholar
  37. 37.
    Alvarez-Fischer D, Henze C, Strenzke C, Westrich J, Ferger B, Höglinger GU, Oertel WH, Hartmann A (2008) Characterization of the striatal 6-OHDA model of Parkinson’s disease in wild type and α-synuclein-deleted mice. Exp Neurol 210(1):182–193. doi: 10.1016/j.Expneurol.2007.10.012 CrossRefPubMedGoogle Scholar
  38. 38.
    Deutch AY, Goldstein M, Baldino F Jr, Roth RH (1988) Telencephalic projections of the A8 dopamine cell group. Ann N Y Acad Sci 537:27–50CrossRefPubMedGoogle Scholar
  39. 39.
    Vollbrecht PJ, Simmler LD, Blakely RD, Deutch AY (2014) Dopamine denervation of the prefrontal cortex increases expression of the astrocytic glutamate transporter GLT-1. J Neurochem 130(1):109–114. doi: 10.1111/jnc.12697 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kipp M, Kiessling MC, Hochstrasser T, Roggenkamp C, Schmitz C (2017) Design-based stereology for evaluation of histological parameters. J Mol Neurosci 61(3):325–342. doi: 10.1007/s12031-016-0858-9 CrossRefPubMedGoogle Scholar
  41. 41.
    Block ML, Hong J-S (2005) Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76(2):77–98. doi: 10.1016/j.pneurobio.2005.06.004 CrossRefPubMedGoogle Scholar
  42. 42.
    Streit WJ (1996) The role of microglia in brain injury. Neurotoxicology 17(3–4):671–678PubMedGoogle Scholar
  43. 43.
    Dutra MF, Jaeger M, Ilha J, Kalil-Gaspar PI, Marcuzzo S, Achaval M (2012) Exercise improves motor deficits and alters striatal GFAP expression in a 6-OHDA-induced rat model of Parkinson’s disease. Neurol Sci 33(5):1137–1144. doi: 10.1007/s10072-011-0925-5 CrossRefPubMedGoogle Scholar
  44. 44.
    Anastasia A, Torre L, de Erausquin GA, Masco DH (2009) Enriched environment protects the nigrostriatal dopaminergic system and induces astroglial reaction in the 6-OHDA rat model of Parkinson’s disease. J Neurochem 109(3):755–765. doi: 10.1111/j.1471-4159.2009.06001.x CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Henning J, Strauss U, Wree A, Gimsa J, Rolfs A, Benecke R, Gimsa U (2008) Differential astroglial activation in 6-hydroxydopamine models of Parkinson's disease. Neurosci Res 62(4):246–253. doi: 10.1016/j.neures.2008.09.001 CrossRefPubMedGoogle Scholar
  46. 46.
    Chaudhuri KR, Healy DG, Schapira AHV (2006) Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 5(3):235–245. doi: 10.1016/S1474-4422(06)70373-8 CrossRefPubMedGoogle Scholar
  47. 47.
    Chaudhuri KR, Sauerbier A (2015) Parkinson disease: unravelling the nonmotor mysteries of Parkinson disease. Nat Rev Neurol 12(1):10–11. doi: 10.1038/nrneurol.2015.236 CrossRefGoogle Scholar
  48. 48.
    Hely MA, Morris JGL, Reid WGJ, Trafficante R (2005) Sydney multicenter study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord: Off J Mov Disord Soc 20(2):190–199. doi: 10.1002/mds.20324 CrossRefGoogle Scholar
  49. 49.
    Christopher L, Duff-Canning S, Koshimori Y, Segura B, Boileau I, Chen R, Lang AE, Houle S et al (2015) Salience network and parahippocampal dopamine dysfunction in memory-impaired Parkinson disease. Ann Neurol 77(2):269–280. doi: 10.1002/ana.24323 CrossRefPubMedGoogle Scholar
  50. 50.
    Christopher L, Marras C, Duff-Canning S, Koshimori Y, Chen R, Boileau I, Segura B, Monchi O et al (2014) Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson’s disease with mild cognitive impairment. Brain 137(Pt 2):565–575. doi: 10.1093/brain/awt337 CrossRefPubMedGoogle Scholar
  51. 51.
    Apitz T, Bunzeck N (2013) Dopamine controls the neural dynamics of memory signals and retrieval accuracy. Neuropsychopharmacology 38(12):2409–2417. doi: 10.1038/npp.2013.141 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Alexander GE (2004) Biology of Parkinson’s disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Dialogues Clin Neurosci 6(3):259–280PubMedPubMedCentralGoogle Scholar
  53. 53.
    Blandini F, Armentero MT (2012) Animal models of Parkinson’s disease. FEBS J 279(7):1156–1166. doi: 10.1111/j.1742-4658.2012.08491.x CrossRefPubMedGoogle Scholar
  54. 54.
    Bove J, Perier C (2012) Neurotoxin-based models of Parkinson’s disease. Neuroscience 211:51–76. doi: 10.1016/j.neuroscience.2011.10.057 CrossRefPubMedGoogle Scholar
  55. 55.
    Ungerstedt U (1968) 6-hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 5(1):107–110. doi: 10.1016/0014-2999(68)90164-7 CrossRefPubMedGoogle Scholar
  56. 56.
    Berger K, Przedborski S, Cadet JL (1991) Retrograde degeneration of nigrostriatal neurons induced by intrastriatal 6-hydroxydopamine injection in rats. Brain Res Bull 26(2):301–307. doi: 10.1016/0361-9230(91)90242-C CrossRefPubMedGoogle Scholar
  57. 57.
    Tatenhorst L, Tonges L, Saal KA, Koch JC, Szego EM, Bahr M, Lingor P (2014) Rho kinase inhibition by fasudil in the striatal 6-hydroxydopamine lesion mouse model of Parkinson disease. J Neuropathol Exp Neurol 73(8):770–779. doi: 10.1097/nen.0000000000000095 CrossRefPubMedGoogle Scholar
  58. 58.
    He Y, Appel S, Le W (2001) Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res 909(1–2):187–193CrossRefPubMedGoogle Scholar
  59. 59.
    Spieles-Engemann AL, Behbehani MM, Collier TJ, Wohlgenant SL, Steece-Collier K, Paumier K, Daley BF, Gombash S et al (2010) Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss. Neurobiol Dis 39(1):105–115. doi: 10.1016/j.nbd.2010.03.009 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Luft AR, Schwarz S (2009) Dopaminergic signals in primary motor cortex. Int J Dev Neurosci 27(5):415–421. doi: 10.1016/j.ijdevneu.2009.05.004 CrossRefPubMedGoogle Scholar
  61. 61.
    Moore RY, Whone AL, Brooks DJ (2008) Extrastriatal monoamine neuron function in Parkinson’s disease: an 18F-dopa PET study. Neurobiol Dis 29(3):381–390. doi: 10.1016/j.nbd.2007.09.004 CrossRefPubMedGoogle Scholar
  62. 62.
    Fukuda T, Takahashi J, Tanaka J (1999) Tyrosine hydroxylase-immunoreactive neurons are decreased in number in the cerebral cortex of Parkinson’s disease. Neuropathology 19(1):10–13. doi: 10.1046/j.1440-1789.1999.00196.x CrossRefPubMedGoogle Scholar
  63. 63.
    Haas SJ, Zhou X, Machado V, Wree A, Krieglstein K, Spittau B (2016) Expression of Tgfbeta1 and inflammatory markers in the 6-hydroxydopamine mouse model of Parkinson’s disease. Front Mol Neurosci 9:7. doi: 10.3389/fnmol.2016.00007 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Fan XT, Zhao F, Ai Y, Andersen A, Hardy P, Ling F, Gerhardt GA, Zhang Z et al (2014) Cortical glutamate levels decrease in a non-human primate model of dopamine deficiency. Brain Res 1552:34–40. doi: 10.1016/j.brainres.2013.12.035 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Jan C, Pessiglione M, Tremblay L, Tande D, Hirsch EC, Francois C (2003) Quantitative analysis of dopaminergic loss in relation to functional territories in MPTP-treated monkeys. Eur J Neurosci 18(7):2082–2086CrossRefPubMedGoogle Scholar
  66. 66.
    Halje P, Tamtè M, Richter U, Mohammed M, Cenci MA, Petersson P (2012) Levodopa-induced dyskinesia is strongly associated with resonant cortical oscillations. J Neurosci: Off J Soc Neurosci 32(47):16541–16551. doi: 10.1523/JNEUROSCI.3047-12.2012 CrossRefGoogle Scholar
  67. 67.
    Debeir T, Ginestet L, François C, Laurens S, Martel J-C, Chopin P, Marien M, Colpaert F et al (2005) Effect of intrastriatal 6-OHDA lesion on dopaminergic innervation of the rat cortex and globus pallidus. Exp Neurol 193(2):444–454. doi: 10.1016/j.expneurol.2005.01.007 CrossRefPubMedGoogle Scholar
  68. 68.
    Lindenbach D, Conti MM, Ostock CY, Dupre KB, Bishop C (2015) Alterations in primary motor cortex neurotransmission and gene expression in hemi-Parkinsonian rats with drug-induced dyskinesia. Neuroscience. doi: 10.1016/j.neuroscience.2015.09.018
  69. 69.
    Guo L, Xiong H, Kim J-I, Wu Y-W, Lalchandani RR, Cui Y, Shu Y, Xu T et al (2015) Dynamic rewiring of neural circuits in the motor cortex in mouse models of Parkinson’s disease. Nat Neurosci 18(9):1299–1309. doi: 10.1038/nn.4082 http://www.nature.com/neuro/journal/v18/n9/abs/nn.4082.html#supplementary-information CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Deutch AY, Goldstein M, Baldino F, Roth RH (1988) Telencephalic projections of the A8 dopamine cell group. Ann N Y Acad Sci 537:27–50CrossRefPubMedGoogle Scholar
  71. 71.
    Clarner T, Janssen K, Nellessen L, Stangel M, Skripuletz T, Krauspe B, Hess FM, Denecke B et al (2015) CXCL10 triggers early microglial activation in the cuprizone model. J Immunol 194(7):3400–3413. doi: 10.4049/jimmunol.1401459 CrossRefPubMedGoogle Scholar
  72. 72.
    Clarner T, Diederichs F, Berger K, Denecke B, Gan L, van der Valk P, Beyer C, Amor S et al (2012) Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions. Glia 60(10):1468–1480. doi: 10.1002/glia.22367 CrossRefPubMedGoogle Scholar
  73. 73.
    Gervasi NM, Scott SS, Aschrafi A, Gale J, Vohra SN, MacGibeny MA, Kar AN, Gioio AE et al (2016) The local expression and trafficking of tyrosine hydroxylase mRNA in the axons of sympathetic neurons. RNA (New York, NY) 22(6):883–895. doi: 10.1261/rna.053272.115 CrossRefGoogle Scholar
  74. 74.
    Godena VK, Brookes-Hocking N, Moller A, Shaw G, Oswald M, Sancho RM, Miller CC, Whitworth AJ et al (2014) Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations. Nat Commun 5:5245. doi: 10.1038/ncomms6245 CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Volpicelli-Daley LA, Gamble KL, Schultheiss CE, Riddle DM, West AB, Lee VM (2014) Formation of alpha-synuclein Lewy neurite-like aggregates in axons impedes the transport of distinct endosomes. Mol Biol Cell 25(25):4010–4023. doi: 10.1091/mbc.E14-02-0741 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Lamberts JT, Hildebrandt EN, Brundin P (2015) Spreading of alpha-synuclein in the face of axonal transport deficits in Parkinson’s disease: a speculative synthesis. Neurobiol Dis 77:276–283. doi: 10.1016/j.nbd.2014.07.002 CrossRefPubMedGoogle Scholar
  77. 77.
    McDowell K, Chesselet MF (2012) Animal models of the non-motor features of Parkinson’s disease. Neurobiol Dis 46(3):597–606. doi: 10.1016/j.nbd.2011.12.040 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Birte Becker
    • 1
  • Melek Demirbas
    • 1
  • Sonja Johann
    • 1
  • Adib Zendedel
    • 1
    • 2
  • Cordian Beyer
    • 1
  • Hans Clusmann
    • 3
  • Stefan Jean-Pierre Haas
    • 4
  • Andreas Wree
    • 4
  • Sonny Kian Hwie Tan
    • 3
  • Markus Kipp
    • 5
  1. 1.Institute of Neuroanatomy, Faculty of MedicineRWTH Aachen UniversityAachenGermany
  2. 2.Department of Anatomical Sciences, Faculty of MedicineGiulan University of Medical SciencesRashtIran
  3. 3.Department of Neurosurgery, Uniklinik RWTH AachenAachenGermany
  4. 4.Institute of AnatomyRostock University Medical CenterRostockGermany
  5. 5.Department of Anatomy IILudwig-Maximilians-University of MunichMunichGermany

Personalised recommendations