Acta Neuropathologica

, Volume 78, Issue 5, pp 543–550

Immunohistochemical visualization of afferent nerve terminals in human globus pallidus and its alteration in neostriatal neurodegenerative disorders

  • S. Goto
  • A. Hirano
  • R. R. Rojas-Corona
Regular Papers


The afferent nerve terminal in the human globus pallidus, which receives the projection nerve fibers from both the striatum and the subthalamic nucleus, were clearly visualized immunohistochemically using antibodies to calcineurin, synaptophysin, Met-enkephalin (MEnk) and substance P (SP). In normal control case, MEnk and SP-like immunoreactivities were densely localized in the external and internal pallidal segments, respectively, whereas calcineurin and synaptophysin were distributed throughout the globus pallidus. Calcineurin, synaptophysin, MEnk and SP-like immunoreactive peroxidase products decorated most of the long radiating dendrites and the cell bodies of the pallidal neurons. In the cases with Huntington's disease (HD) and striatonigral degeneration (SND), marked loss of calcineurin, MEnk and SP-like immunoreactivities was seen in the globus pallidus corresponding to areas of striatal neurodegeneration, whereas synaptophysin immunoreactivity remained in areas which revealed almost complete loss of calcineurin, MEnk and SP-like immunoreactivities. Calcineurin, MEnk and SP, which show difference in their localization patterns, may provide reliable markers for the striatal efferent nerve terminals, and synaptophysin for the entire pallidal afferent nerve terminals. This report demonstrates the distribution patterns of these neurochemical molecules in the globus pallidus with HD and SND.

Key words

Globus pallidus Immunohistochemistry Calcineurin Synaptophysin Neuropeptides 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adams RD (1968) The striatonigral degeneration. Clin Neurol 6:694–702Google Scholar
  2. 2.
    Bolam JP (1984) Synapses of identified neurons in the neostriatum. Ciba Found Symp 107:30–47Google Scholar
  3. 3.
    Bolam JP, Somogyi P, Takagi H, Fodor I, Smith AD (1983) Localization of substance P-like immunoreactivity in neurons and nerve terminals in the neostriatum of the rat: a correlated light and electron microscopic study. J Neurocytol 12:325–344Google Scholar
  4. 4.
    Bruyn GW (1968) Disease of basal ganglia. Clin Neurol 6:298–378Google Scholar
  5. 5.
    Carpenter MB, Strominger NL (1967) Efferent fiber projections of the subthalamic nucleus in the rhesus monkey. Am J Anat 121:41–72Google Scholar
  6. 6.
    Chesselet M-F, Graybiel AM (1983) Subdivisions of the pallidum and the substantia nigra demonstrated by immunohistochemistry. Neurosci Abstr 9:16Google Scholar
  7. 7.
    Del Fiacco M, Paxinos G, Cuello AC (1982) Neostriatal enkephalin-immunoreactive neurons project to the globus pallidus. Brain Res 231:1–17Google Scholar
  8. 8.
    Deniau JM, Chevalier G (1984) Synaptic organization of the basal ganglia: an electroanatomical approach in the cat. Ciba Found 107:48–63Google Scholar
  9. 9.
    Emson PC, Arregui A, Clement-Jones V, Sandberg BEB, Rossor M (1980) Regional distribution of methionineenkephalin and substance P-like immunoreactivity in normal human brain and in Huntington's disease. Brain Res 199:147–160Google Scholar
  10. 10.
    Fox CA, Rafols JA (1975) The radial fibers in the globus pallidus. J Comp Neurol 159:177–200Google Scholar
  11. 11.
    Fox CA, Rafols JA (1976) The striatal efferents in the globus pallidus and in the substantia nigra. In: Yahr MD (ed) The basal ganglia. Association for research in nervous and mental disease, vol 55, Raven Press, New York, pp 37–55Google Scholar
  12. 12.
    Fox CA, Rafols JA, Cowan WM (1975) Computer measurements of axis cylinder diameters of radial fibers and “comb”-bundle fibers. J Comp Neurol 159:201–224Google Scholar
  13. 13.
    Gebbink THB (1968) Huntington's chorea: Fibre changes in the basal ganglia. Handb Clin Neurol 6:399–408Google Scholar
  14. 14.
    Goto S, Yamamoto H, Fukunaga K, Iwasa T, Matsukado Y, Miyamoto E (1985) Dephosphorylation of microtubuleassociated protein 2, tau factor and tubulin by calcineurin. J Neurochem 45:276–283Google Scholar
  15. 15.
    Goto S, Matsukado Y, Mihara Y, Inoue N, Miyamoto E (1986) Calcineurin as a neuronal marker of human brain tumor. Brain Res 371:237–243Google Scholar
  16. 16.
    Goto S, Matsukado Y, Mihara Y, Inoue N, Miyamoto E (1986) The distribution of calcineurin in the rat brain by light and electron microscopic immunohistochemistry and enzyme-immunoassay. Brain Res 397:161–172Google Scholar
  17. 17.
    Goto S, Matsukato Y, Mihara Y, Inoue N, Miyamoto E (1986) Calcineurin in human brain and its relation to extrapyramidal system. Immunohistochemical study on postmortem brains. Acta Neuropathol (Berl) 72:150–156Google Scholar
  18. 18.
    Goto S, Matsukado Y, Miyamoto E, Yamada M (1987) Morphological characterization of the striatal neurons expressing calcineurin immunoreactivity. Neuroscience 22:189–201Google Scholar
  19. 19.
    Goto S, Matsukado Y, Mihara Y, Inoue N, Miyamoto E (1987) Immunocytochemical demonstration of calcineurin in human nerve cell tumors. Cancer 60:2948–2957Google Scholar
  20. 20.
    Goto S, Matsukado Y, Uemura S, Mihara Y, Inoue N, Ikeda J, Miyamoto E (1988) A comparative immunohistochemical study on calcineurin and S-100 protein in mammalian and avian brains. Exp Brain Res 69:645–650Google Scholar
  21. 21.
    Goto S, Hirano A, Rojas-Corona RR (1989) Calcineurin immunoreactivity in striatonigral degeneration. Acta Neuropathol 78:65–71Google Scholar
  22. 22.
    Goto S, Hirano A, Rojas-Corona RR (1989) An immunohistochemical investigation of the human neostriatum in Huntington's disease. Ann Neurol 25:298–304Google Scholar
  23. 23.
    Grafe MR, Forno LS, Eng LF (1985) Immunocytochemical studies of substance P and met-enkephalin in the basal ganglian and substantia nigra in Huntington's, Parkinson's and Alzheimer's disease. J Neuropathol Exp Neurol 44:47–59Google Scholar
  24. 24.
    Graybiel AM (1983) Compartmental organization of the mammalian striatum. Prog Brain Res 58:247–256Google Scholar
  25. 25.
    Graybiel AM (1984) Neurochemically specified subsystems in the basal ganglia. Ciba Found Symp 107:114–149Google Scholar
  26. 26.
    Graybiel AM (1986) Neuropeptides in the basal ganglia. In: Martin JB, Barchas JD (eds) Neuropeptides in neurologic and psychiatric disease. Association for research in nervous and mental disease, vol 64. Raven Press, New York, pp 135–161Google Scholar
  27. 27.
    Haber SN, Elde RP (1981) Correlation between metenkephalin and substance P immunoreactivity in the primate globus pallidus. Neuroscience 6:1291–1297Google Scholar
  28. 28.
    Haber SN, Nauta WJH (1983) Ramifications of the globus pallidus in the rat as indicated by patterns of immunohistochemistry. Neuroscience 9:245–260Google Scholar
  29. 29.
    Hsu S, Raine L, Fanger H (1981) Use of avidin-biotinperoxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 29:577–580Google Scholar
  30. 30.
    Jahn R, Schiebler W, Quimet C, Greengard P (1985) A 38,000-dalton membrane protein (p38) present in synaptic vesicles. Proc Natl Acad Sci USA 82:4137–4141Google Scholar
  31. 31.
    Kanazawa I, Bird E, O'Connell R, Powell D (1977) Evidence for a decrease in Substance P content of substantia nigra in Huntington's chorea. Brain Res 120:387–392Google Scholar
  32. 32.
    Klee CB, Krinks MH, Manalan AS, Cohen P, Stewart AA (1983) Isolation and characterization of bovine calcineurin: a calmodulin-stimulated protein phosphate. Methods Enzymol 102:227–244Google Scholar
  33. 33.
    Nauta WJH (1979) Projections of the pallidal complex: autoradiographic studies in the cat. Neuroscience 4:1853–1873Google Scholar
  34. 34.
    Nauta WJH, Cole M (1979) Efferent projections of the subthalamic nucleus: an autoradiographic study in monkey and cat. J Comp Neurol 180:1–16Google Scholar
  35. 35.
    Nauta WJH, Domesick VB (1984) Afferent and efferent relationships of the basal ganglia. Ciba Found Symp 107:3–29Google Scholar
  36. 36.
    Nauta WJH, Mehler WR (1966) Projections of the lentiform nucleus in the monkey. Brain Res 1:3–42Google Scholar
  37. 37.
    Reiner A, Albin RL, Anderson KD, D'Amato CJ, Penney JB, Young AB (1988) Differential loss of striatal projection neurons in Huntington's disease. Proc Natl Acad Sci USA 85:5733–5737Google Scholar
  38. 38.
    Scheibel ME, Scheibel AB (1966) The organization of the nucleus renticularis thamali: a Golgi study. Brain Res 1:43–62Google Scholar
  39. 39.
    Vonsattel J-P, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP (1985) Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol 44:559–577Google Scholar
  40. 40.
    Wallace RW, Tallant EA, Cheung WY (1980) High levels of a heat-labile calmodulin-binding protein (CaM-BPSO) in bovine neostriatum. Biochemistry 19:1831–1837Google Scholar
  41. 41.
    Wiedemann B, Franke WW (1985) Identification and localization of synaptophysin, an integral membrane glycoprotein ofM r 38,000 characteristic of presynaptic vesicles. Cell 41:1017–1028Google Scholar
  42. 42.
    Wilson SAK (1914) An experimental research into the anatomy and physiology of the corpus striatum. Brain 36:427–492Google Scholar
  43. 43.
    Wood JG, Wallace RW, Whitaker JN, Cheung WY (1980) Immunohistochemical localization of calmodulin and a heat-labile calmodulin-binding protein (CaM-BPSO) in basal ganglia of mouse brain. J Cell Biol 84:66–76Google Scholar

Copyright information

© Springer-Verlag GmbH & Co. KG 1989

Authors and Affiliations

  • S. Goto
    • 1
  • A. Hirano
    • 1
  • R. R. Rojas-Corona
    • 2
  1. 1.Division of Neuropathology Department of Pathology, Montefiore Medical CenterAlbert Einstein College of MedicineBronxUSA
  2. 2.Division of Immunopathology, Department of Pathology, Montefiore Medical CenterAlbert Einstein College of MedicineBronxUSA

Personalised recommendations