Acta Neuropathologica

, Volume 83, Issue 4, pp 352–360 | Cite as

Caudate nucleus pathology in Parkinson's disease: ultrastructural and biochemical findings in biopsy material

  • B. Lach
  • D. Grimes
  • B. Benoit
  • A. Minkiewicz-Janda
Regular Papers


Ultrastructural and biochemical properties of caudate nucleus (CN) biopsies in two patients with advanced Parkinson's disease (PD) were compared with three CN specimens removed during surgery for intracranial tumors. An additional two specimens from neurologically intact patients (59 and 86 years old) were removed during autopsy (performed 3 and 4 h post mortem, respectively) for electron microscopic studies. Dopamine levels in PD were reduced to less than 15% of control values. Both PD patients showed frequent dystrophic neurites and transsynaptic degeneration of neurons and neuritic processes. These changes were not found in CN from the four control individuals. Only a few dystrophic neurites were noticed in one 67-year-old control patient. The development of neuroaxonal dystrophy in CN is consistent with a dying-back process, probably accompanying abnormalities of axonal transport in PD. Transsynaptic degeneration of neurons in CN very likely represents a morphological marker of disease severity. The occurrence of this change may account for the poor clinical response of patients with advanced PD to intracerebral implantation of dopaminergic tissues.

Key words

Parkinson's disease Ultrastructure Catecholomines Trans-synaptic degeneration Axonal dystrophy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allen RD, Weiss DG, Hayden JH, Brown DT, Fujiwake H, Simpson M (1985) Gliding movement of and bidirectional transport along single native microtubules from squid axoplasm: evidence for an active role of microtubules in cytoplasmic transport. J Cell Biol 100:1736–1752Google Scholar
  2. 2.
    Backlund EO, Greenberg PO, Hamberger B, Knutsson E, Martensson A, Sedvall G, Seiger A, Olson L (1985) Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trial. J Neurosurg 62:169–173Google Scholar
  3. 3.
    Bancher C, Lassmann H, Budka H, Jellinger K, Grundke-Iqbal I, Iqbal K, Wiche G, Seitelbeger F, Wisniewski HM (1989) An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination. J Neuropathol Exp Neurol 48:81–93Google Scholar
  4. 4.
    Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. J Neurol Sci 20:415–455Google Scholar
  5. 5.
    Blakemore WF, Cavanagh JB (1969) “Neuroaxonal dystrophy” occurring in an experimental “dying back” process in the rat. Brain 92:790–811Google Scholar
  6. 6.
    Bouyer JJ, Park DH, Joh TH, Pickel VM (1984) Chemical and structural analysis of the relation between cortical input and tyrosine hydroxylase containing terminals in rat neostriatum. Brain Res 302:267–275Google Scholar
  7. 7.
    Bugiani O, Perdelli F, Slavarani S, Leonardi A, Mancardi GL (1980) Loss of striatal neurons in Parkinson's disease: a cytometric study. Eur Neurol 19:339–344Google Scholar
  8. 8.
    Chou SM, Hartmann HA (1965) Electron Microscopy of focal neuroaxonal lesions produced by B,B1-iminodiproprionitrile (IDPN) in rats. Acta Neuropathol 4:590–603Google Scholar
  9. 9.
    Chung YW, Hasler RG (1984) Types of synapses in the pallidum and their differential degeneration following lesions of pallidal afferents in squirrel monkey (Saimiri sciurus). Adv Neurol 40:21–27Google Scholar
  10. 10.
    de Coster W, Roels H, Van der Eecken H (1971) Electron microscopical study of neuroaxonal dystrophy. Eur Neurol 5:65–83Google Scholar
  11. 11.
    Dickson DW, Wertkin A, Kress Y, Ksiezak-Reding H, Wen SH (1990) Ubiquitin immunoreactive structures in normal human brains. Distribution and developmental aspects. Lab Invest 63:87–99Google Scholar
  12. 12.
    Duffy P, Tennyson VM (1965) Phase and electronmicroscopic observations of Lewy bodies and melanin granules in the substantia nigra and locus ceruleus in Parkinson's disease. J Neuropathol Exp Neurol 24:398–414Google Scholar
  13. 13.
    Ehringer M, Hornykiewicz O (1950) Verteilung von Noradrenalin und Dopamin im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyamidalen Systems. Klin Wochenschr 38:12–36Google Scholar
  14. 14.
    Forno SF (1986) The Lewy body in Parkinson's disease. Adv Neurol 45:35–43Google Scholar
  15. 15.
    Forno LS, Langston JW (1991) Unfavorable outcome of adrenal medullary transplant for Parkinson's disease. Acta Neuropathol 81:691–694Google Scholar
  16. 16.
    Forno LS, Norville RL (1979) Ultrastructure of neostriatum in Huntington's and Parkinson's disease. Adv Neurol 23:123–135Google Scholar
  17. 17.
    Forno LS, Sternberger LA, Sternberger NH, Strefling AM, Swanson K, Eng L (1986) Reaction of Lewy bodies with antibodies to phosphorylated and non-phosphorylated neurofilaments. Neurosci Lett 64:253–258Google Scholar
  18. 18.
    Freund TF, Powell JF, Smith AD (1984) Tyrosine hydroxylase-immunoreactive boutons in synaptic contacts with identified striato-nigral neurons, with particular reference to dendritic spines. Neuroscience 13:1189–1215Google Scholar
  19. 19.
    Fujisawa K, Shiraki H (1978) Study of axonal dystrophy. I. Pathology of the neuropil of the gracile and cuneate nuclei in ageing and old rats: a sterological study. Neuropathol Appl Neurobiol 4:1–20Google Scholar
  20. 20.
    Gajdusek DC (1985) Hypothesis: interference with axonal transport of neurofilament as a common pathogenetic mechanism in certain diseases of the central nervous system. N Engl J Med 312:714–719Google Scholar
  21. 21.
    Ghetti B, Wisniewski HM (1972) On degeneration of terminals in the cat striate cortex. Brain Res 44:630–635Google Scholar
  22. 22.
    Goldman JE (1987) Cytoskeletal abnormalities in Parkinson's disease. Adv Behav Biol 34:191–197Google Scholar
  23. 23.
    Goldstein M, Liebermann AN, Helmer E, Koslow M, Ransohoff J, Elsworth JD, Roth RH, Deutch AY (1988) Biochemical analysis of caudate nucleus biopsy samples from Parkinsonian patients. Ann Neurol 24:685–688Google Scholar
  24. 24.
    Gray EG, Hamlyn LH (1962) Electronmicroscopy of experimental degeneration in the avian optic tectum. J Anat 96:111–182Google Scholar
  25. 25.
    Griffin JW, Price DL, Engel WR, Drachman D (1977) The pathogenesis of reactive axonal swellings: role of axonal transport. J Neuropathol Exp Neurol 36:214–227Google Scholar
  26. 26.
    Griffin JW, Fahnestock KE, Price DL, Cork LC (1983) Cytoskeletal disorganization induced by local application of B,B1-iminodiproprionitrile and 2,5-hexanedione. Ann Neurol 14:55–61Google Scholar
  27. 27.
    Hassler R, Chung JW, Rinne U, Wagner A (1973) Selective degeneration of two out of nine types of synapses in cat caudate nucleus after cortical lesions. Exp Brain Res 31:67–80Google Scholar
  28. 28.
    Heidelberg-White ET, Floyd MB, Gilles H, Uzman GB (1968) Infantile neuroaxonal dystrophy. A disease characterized by altered terminal axons and synaptic endings. Neurology 18:891–906Google Scholar
  29. 29.
    Hornykiewicz O, Kish SJ (1986) Biochemical pathophysiology of Parkinson's disease. Adv Neurol 45:19–34Google Scholar
  30. 30.
    Hornykiewicz O, Pifl C, Schingnitz G, Kish SJ (1988) The cause of Parkinson's disease: MPTP, aging and the striatal dopamine loss. In: Noppi G, Hornykiewicz O, Fariello RG, et al (eds) Neurodegenerative disorders: the role played by endotoxins and xenobiotics. Raven Press, New York, pp 73–80Google Scholar
  31. 31.
    Hurtig H, Joyce J, Sladek J, Trojanowski JQ (1989) Postmortem analysis of adrenal-medulla-to-caudate autograft in a patient with Parkinson's disease. Ann Neurol 25:607–614Google Scholar
  32. 32.
    Javoy-Agid F, Ruberg M, Taquet H, Bokobza B, Agid Y, Gaspar P, Berger B, N'Guyen-Legros N, Alvarez C, Gray F, Escourolle R, Scatton B, Rouquier L (1984) Biochemical neuropathology of Parkinson's disease. Adv Neurol 40:189–198Google Scholar
  33. 33.
    Jellinger K (1973) Neuroaxonal dystrophy: its natural history and related disorders. Progr Neuropathol 2:129–180Google Scholar
  34. 34.
    Jellinger K (1987) Pathology of parkinsonism. In: Marsden CD, Fahn S (eds) Movement disorders, vol 2. Butterworth, London, pp 124–165Google Scholar
  35. 35.
    Jellinger K, Armstrong D, Zoghbi HY, Percy AK (1988) Neuropathology of Rett syndrome. Acta Neuropathol 76:142–158Google Scholar
  36. 36.
    Jones WH, Thomas DB (1962) Changes in the dendritic organization of neurons in the cerebral cortex following deafferentiation. J Anat 96:375–398Google Scholar
  37. 37.
    Kish SJ, Rajput A, Gilbert J, Rozdilsky B, Chang Li-Jan, Shannak K, Hornykiewicz O (1986) Elevated aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson's disease: correlation with striatal dopamine loss. Ann Neurol 20:26–31Google Scholar
  38. 38.
    Kish SJ, Shannak K, Hornykiewicz O (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. N Engl J Med 319:876–880Google Scholar
  39. 39.
    Lampert PW (1967) A comparitive electronmicroscopic study of reactive, degenerating, regenerating and dystrophic axons. J Neuropathol Exp Neurol 26:345–368Google Scholar
  40. 40.
    Lange HN, Bogerts B (1982) Postencephalitic and idiopathic Parkinsonism. Quantitative changes of tel-, di-, mesencephalum and basal ganglia. Neuroscience [Suppl] 17:127 (A)Google Scholar
  41. 41.
    Lewy FH (1913) Zur pathologischen Anatomie der Paralysis agitans. Dtsch Z Nervenheilke 50:50–55Google Scholar
  42. 42.
    MacDowell CM (1978) Fixation and processing. In: Trump BJ, Jones RT (eds) Diagnostic electron microscopy. Wiley Medical, Toronto, pp 113–140Google Scholar
  43. 43.
    Madrazo I, Druker-Colin R, Diaz V, Martinex-Mata J, Torres C, Becerril JJ (1987) Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson's disease. N Engl J Med 316:831–834Google Scholar
  44. 44.
    Mann DMA, Yates PO (1983) Pathological basis for neurotransmitter changes in Parkinson's disease. Neuropathol Appl Neurobiol 9:3–19Google Scholar
  45. 45.
    McNeill TH, Brown SA, Shoulson I, Lapham LW, Eskin TA, Rafols JA (1987) Regression of striatal dendrites in Parkinson's disease. In: Carpenter MB, Jayaraman A (eds) The basal ganglia, vol 2; structure and function. Plenum Press, New York, pp 475–482Google Scholar
  46. 46.
    Miller RH, Lasek RJ (1985) Cross bridges mediate anterograde and retrograde vesicle transport along microtubules in squid axoplasm. J Cell Biol 101:2181–2193Google Scholar
  47. 47.
    Nakamura Y (1982) Familial neuroaxonal dystrophy with principal lesions of nigro-pallido-subthalamic degeneration. Folia Psychiatr Neurol Jpn 36:151–162Google Scholar
  48. 48.
    Nyberg P, Nordbert A, Webster P, Windblad B (1983) Dopaminergic deficiency is more pronounced in putamen than in nucleus caudatus in Parkinson's disease. Neurochem Pathol 1:193–202Google Scholar
  49. 49.
    Papolla MA (1986) Lewy bodies of Parkinson's disease. Immune electron microscopic demonstration of neurofilament antigens in constituent filaments. Arch Pathol Lab Med 110:1160–1163Google Scholar
  50. 50.
    Pearson J (1983) Neurotransmitter immunocytochemistry in the study of human development, anatomy and pathology. Prog Neuropathol 5:41–97Google Scholar
  51. 51.
    Perlmutter JS (1988) New insights into the pathophysiology of Parkinson's disease: the challenge of positron emission tomography. Trend Neurosci 11:203–208Google Scholar
  52. 52.
    Peters A, Palay SL, Webster H, De F (1976) The fine structure of the nervous system. The neurons and supporting cells. W. B. Saunders, Toronto, pp 118–169Google Scholar
  53. 53.
    Pickel VM, Beckley SC, Joh TH, Reis DJ (1981) Ultrastructural immunocytochemical localization of tyrosine hydroxylase in the neostriatum. Brain Res 225:373–385Google Scholar
  54. 54.
    Politis MJ, Pellegrino RG, Spence PS (1978) Ultrastructural studies of the dying back process. V. axonal neurofilament accumulation at the sites of 2,5-hexamenodione application: evidence for nerve fiber dysfunction in experimental hexocarbon neuropathy. J Neurocytol 9:505–516Google Scholar
  55. 55.
    Prineas J (1969) The pathogenesis of dying back polyneuropathies. I. An ultrastructural study of experimental triortho-cresyl phosphate intoxication in the cat. J Neuropathol Exp Neurol 28:571–597Google Scholar
  56. 56.
    Prineas J (1969) The pathogenesis of dying back polyneuropathies. II. Ultrastructural study of experimental acrylamide intoxication in the cat. J Neuropathol Exp Neurol 28:598–621Google Scholar
  57. 57.
    Sandbank U, Lerman P, Giefman M (1970) Infantile neuroaxonal dystrophy: cortical axonic and presynaptic changes. Acta Neuropathol (Berl) 16:342–352Google Scholar
  58. 58.
    Scatton B, Javoy-Agid F, Moutfort JC, Agid Y (1984) Neurochemistry of monoaminergic neurons in Parkinson's disease. In: Usdin E, Carlsson A, Dahlstorm A, Engel J (eds) Catecholamines: neuropharmacology and central nervous system — Therapeutic aspects. AR Liss, New York, pp 43–52Google Scholar
  59. 59.
    Schnapp BJ, Vale RD, Sheetz MP, Reese TS (1985) Single microtubules from squid axoplasm support bidirectional movement of organelle. Cell 40:4555–4562Google Scholar
  60. 60.
    Seegal FR, Brosch KO, Busch B (1986) High performance liquid chromatography of biogenic amines and metabolites in brain, CSF, urine and plasma. J Chromatogr 377:131–144Google Scholar
  61. 61.
    Seitelberger F (1971) Neuropathological conditions related to neuroaxonal dystrophy. Acta Neuropathol (Berl) [Suppl] V:17–29Google Scholar
  62. 62.
    Shermann D, Desnos C, Darchen F, Pollak P, Javoy-Agid F, Agid Y (1989) Stratal dopamine deficiency in Parkinson's disease: role of aging. Ann Neurol 26:551–557Google Scholar
  63. 63.
    Sotelo C, Palay SL (1971) Altered axons and axon terminals in the lateral vestibular nucleus of the rat. Possible example of axonal remodeling. Lab Invest 215:653–670Google Scholar
  64. 64.
    Spencer PS, Schumberg HH (1976) Central-peripheral axonopathy — The pathology of dying-back polyneuropathies. Prog Neuropathol 8:253–295Google Scholar
  65. 65.
    Stadlan EM, Duvoisin R, Yahr M (1965) The pathology of Parkinsonism. Excerpta Med Int Congr Ser 100:569–571Google Scholar
  66. 66.
    Sung SH (1965) Neuroaxonal dystrophy in aging. Excepta Med Int Congr Ser 100:478–480Google Scholar
  67. 67.
    Tennyson VM, Heikekila R, Mytilineou C, Cote L, Cohen G (1974) 5-Hydroxydopamine “tagged” neuronal boutons in rabbit striatum; inter-relationship between vesicles and axonal membranes. Brain Res 82:342–348Google Scholar
  68. 68.
    Wilson CJ, Groves PM (1980) Fine structure and synaptic connections of the common spinal neurons of neostriatum: as studied employing intracellular injection of horseradish proxidase. J Comp Neurol 194:599–615Google Scholar
  69. 69.
    Voorn P, Buijs RM (1987) Ultrastructural demonstration of dopamine in the central nervous system. In: Steinbuch HWM (ed) Monoaminergic neurons: light microscopy and ultrastructure. J. Wiley and Sons, New York, pp 241–264Google Scholar
  70. 70.
    Zalcman S, Shanks N, Anisman H (1991) Time-dependent variations of central norephinephrine and dopamine following antigen administration. Brain Res (in press)Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • B. Lach
    • 1
  • D. Grimes
    • 2
  • B. Benoit
    • 3
    • 4
  • A. Minkiewicz-Janda
    • 5
  1. 1.Department of Laboratory Medicine, Division of Anatomic Pathology (Neuropathology)Ottawa Civic HospitalOttawaCanada
  2. 2.Division of NeurologyOttawa Civic HospitalOttawaCanada
  3. 3.Division of NeurosurgeryOttawa Civic HospitalOttawaCanada
  4. 4.University of OttawaOttawaCanada
  5. 5.Department of PsychologyCarleton UniversityOttawaCanada

Personalised recommendations