Skip to main content
SpringerLink
Log in

Phosphorylated high molecular weight neurofilament protein in lower motor neurons in amyotrophic lateral sclerosis and other neurodegenerative diseases involving ventral horn cells

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Lower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis (ALS), Werdnig-Hoffmann's disease (WH), X-linked recessive bulbospinal neuronopathy (X-BSNP) and multiple system atrophy (MSA), all of which were known to involve the lower motor neurons, were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments. The incidence of Ta-51-positive neurons was significantly increased in ALS, WH and MSA, but not in X-BSNP. Ta-51-positive neurons showed a wide variety of morphological appearances, including neurons with normal appearance, central chromatolysis, simple atrophy and neurons containing massive neurofilamentous accumulation. In aged-control cases, similar Ta-51-positive neurons were observed, although to a much lesser extent. In ALS, spheroids and globules, which were strongly positive for Ta-51, were also significantly increased. Ta-51-positive motor neurons, spheroids and globules appeared in proportional to the number of remaining large motor neurons in ALS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Binet S, Maininger V (1988) Modifications of microtubule proteins in ALS nerve procede detectable histologic and ultrastructural changes. Neurology 38:1596–1600

    Google Scholar 

  2. Bizzi A, Gambetti P (1986) Phosphorylation of neurofilaments is altered in aluminium intoxication. Acta Neuropathol (Berl) 71:154–158

    Google Scholar 

  3. Breuer AC, Lynn MP, Atkinson MB, Chou SM, Wilbourn AJ, Marks KE, Culver JE, Fleegler EJ (1987) Fast axonal transport in amyotrophic lateral sclerosis: an intra-axonal organelle traffic analysis. Neurology 37:738–748

    Google Scholar 

  4. Carden MJ, Sehlaepfer WW, Lee VM-Y (1985) The structure, biochemical properities and immunogenicity of neurofilament peripheral regions are determined by phosphorylation. J Biol Chem 260:9805–9817

    Google Scholar 

  5. Carden MJ, Trojanowski JQ, Schlaepfer WW, Lee VM-Y (1987) Two-stage expression of neurofilament polypeptide during rat neurogenesis with early establishment of adult phosphorylation patterns. J Neurosci 7:3489–3504

    Google Scholar 

  6. Carpenter S (1968) Proximal axonal enlargement in motor neuron disease. Neurology 18:841–851

    Google Scholar 

  7. Chou SM, Fakadej AV (1971) Ultrastructure of chromatolytic motoneurons and anterior spinal roots in a case of Werdnig-Hoffman disease. J Neuropathol Exp Neurol 30:368–379

    Google Scholar 

  8. Clark AW, Parhad IM, Griffin JW, Price DL (1984) Neurofilamentous axonal swellings as a normal finding in the spinal anterior horn of man and other primates. J Neuropathol Exp Neurol 43:253–262

    Google Scholar 

  9. Cork LC, Sternberger NH, Sternberger LA, Casanova MF, Struble RG, Price DL (1986) Phosphorylated neurofilament antigens in neurofibrillary tangles in Alzheimer's disease. J Neuropathol Exp Neurol 45:56–64

    Google Scholar 

  10. Cork LC, Troncoso JC, Klavano GG, Johnson ES, Sternberger LA, Sternberger NH, Price DL (1988) Neurofilamentous abnormalities in motor neurons in spontaneously occurring animals disorders. J Neuropathol Exp Neurol 47:420–431

    Google Scholar 

  11. Delisle MB, Carpenter S (1984) Neurofibrillary axonal swellings and mayorophic lateral sclerosis. J Neurol Sci 63:241–250

    Google Scholar 

  12. Dickson DW, Yen SH, Suzuki KI, Davies P, Carcia JH, Hirano A (1986) Ballooned neurons in select neurodegenerative diseases contain phosphorylated neurofilament epitopes. Acta Neuropathol (Berl) 71:216–223

    Google Scholar 

  13. Forno LS, Sternberger LA, Sternberger NH, Strefling AM, Swanson K, Eng LF (1986) Reaction of Lewy bodies with antibodies to phosphorylated and nonphosphorylated neurofilaments. Neurosci Lett 64:253–258

    Google Scholar 

  14. Gold BG, Price DL, Griffin JW, Rosenfeld J, Hoffmen PN, Sternberger NH, Sternberger LA (1988) Neurofilament antigens in acrylamide neuropathy. J Neuropathol Exp Neurol 47:145–157

    Google Scholar 

  15. Hirano A (1982) Aspects of the ultrastructure of amyotrophic lateral sclerosis. In: Rowland LP (ed) Human motor neuron disease. Raven Press, New York, pp 75–88

    Google Scholar 

  16. Hirano A, Donnenfeld H, Sasaki S, Nakano I (1984) Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 43:461–470

    Google Scholar 

  17. Konno H, Yamamoto T, Iwasaki Y, Iizuka H (1986) Shy-Drager syndrome and amyotrophic lateral sclerosis: cytoarchitectonic and morphometric studies of sacral autonomic neurons. J Neurol Sci 73:193–204

    Google Scholar 

  18. Kumagai T, Hashizume Y (1982) Morphological and morphometric studies on the spinal cord lesion in Werdnig-Hoffmann disease. Brain Develop 4:87–96

    Google Scholar 

  19. Lee VM-Y, Wu H-L, Schlaepfer WW (1982) Monoclonal antibodies recognize individual neurofilament triplet proteins. Proc Natl Acad Sci USA 79:6089–6092

    Google Scholar 

  20. Lee VM-Y, Carden MJ, Schaepfer WW (1986) Structural similarities and differences between neurofilament proteins from five different species as revealed using monoclonal antibodies. J Neurosci 6:179–188

    Google Scholar 

  21. Lee VM-Y, Carden MJ, Schlaepfer WW, Trojanowski JQ (1987) Monoclonal antibodies distinguish several differentially phosphorylated states of the two largest rat neurofilament subunits (NF-H and NF-M) and demonstrate their existence in the normal nervous system of adult rats. J Neurosci 7:3474–3488

    Google Scholar 

  22. Leigh PN, Dodson A, Swash M, Brion J-P, Anderton BH (1989) Cytoskeletal abnormalities in motor neuron disease, and immunocytochemical study. Brain 112:521–535

    Google Scholar 

  23. Lippa CF, Smith TW (1988) Chromatolytic neurons in Werdnig-Hoffmann disease contain phosphorylated neurofilaments. Acta Neuropathol 77:91–94

    Google Scholar 

  24. Manetto V, Sternberger NH, Perry G, Sternberger LA, Gambetti P (1988) Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 47:642–653

    Google Scholar 

  25. Moss TH, Lewkowicz SJ (1983) The axon reaction in motor and sensory neurons of mice studied by a monoclonal antibody marker of neurofilament protein. J Neurol Sci 61:267–280

    Google Scholar 

  26. Munoz DG, Greene C, Perl DP, Selkoe DJ (1988) Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral scerlosis patients. J Neuropathol Exp Neurol 47:9–18

    Google Scholar 

  27. Rasool CG, Selkoe DJ (1985) Sharing of specific antigens by degenerating neurons in Pick's disease and Alzheimer's disease. N Engl J Med 312:700–705

    Google Scholar 

  28. Rosenfeld J, Dorman ME, Griffin JW, Sternberger LA, Sternberger NH, Price DL (1987) Distribution of neurofilament antigens after axonal injury. J Neuropathol Exp Neurol 46:269–282

    Google Scholar 

  29. Sasaki S, Kamei H, Yamane Y, Maruyama S (1988) Swelling of neuronal processes in motor neuron disease. Neurology 38:1114–1118

    Google Scholar 

  30. Schlaepfer WW (1987) Neurofilaments: structure, metabolism and implication in disease. J Neuropathol Exp Neurol 46:117–129

    Google Scholar 

  31. Schmidt ML, Carden MJ, Lee VMY, Trojanowski JQ (1987) Phosphate dependent and independent neurofilament epitopes in the axonal swellings of patients with motor neuron disease and controls. Lab Invest 56:282–294

    Google Scholar 

  32. Sobue G, Sahashi K, Takahashi A, Matsuoka Y, Muroga T, Sobue I (1983) Degenerating compartment and functioning compartment of motor neurons in ALS: possible process of motor neuron loss. Neurology 33:654–657

    Google Scholar 

  33. Sobue G, Hashizume Y, Ohya M, Takahashi A (1986) Shy-Drager syndrome: Neuronal loss depends on size, function and topography in ventral spinal outflow. Neurology 36:404–407

    Google Scholar 

  34. Sobue G, Yasuda T, Mitsuma T, Ross A, Pleasure D (1988) Expression of nerve growth factor receptors in human peripheral neuropathies. Ann Neurol 24:64–72

    Google Scholar 

  35. Sobue G, Hashizume Y, Mukai E, Hirayama M, Mitsuma T, Takahashi A (1989) X-linked recessive bulbospinal neuronopathy, a clinicopathological study. Brain 112:209–232

    Google Scholar 

  36. Sternberger LA, Sternberger NH (1983) Monoclonal antibodies phosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci USA 80:6126–6130

    Google Scholar 

  37. Sternberger LA, Sternberger NH, Ulrich J (1985) Aberant neurofilament phosphorylation in Alzheimer disease. Proc Natl Acad Sci USA 82:4274–4276

    Google Scholar 

  38. Terao S, Sobue G, Takeda A, Mitsuma T, Takahashi A (1988) Three-dimensional distribution of spinal anterior horn cells in amyotrophic lateral sclerosis and Shy Drager syndrome — A study of cytoarchitectonic feature. Clin Neurol (Tokyo) 28:1178–1187

    Google Scholar 

  39. Toroncoso JC, Sternberger NH, Sternberger LA, Hoffmann PN (1986) Immunocytochemical studies of neurofilament antigens in the neurofibrillary pathology induced by aluminium. Brain Res 364:295–300

    Google Scholar 

  40. Toyoshima I, Yamamoto A, Masamune O, Satake M (1989) Phosphorylation of neurofilament proteins and localization of axonal swellings in motor neuron disease. J Neurol Sci 89:269–277

    Google Scholar 

  41. Trojanowski JQ, Walkenstein N, Lee VMY (1986) Expression of neurofilament subunits in neurons of the central and peripheral nervous system: an immunohistochemical study with monoclonal antibodies. J Neurosci 6:650–662

    Google Scholar 

  42. Wiley CA, Love S, Skoglund RR, Lampert PW (1987) Infantile neurodegenerative disease with neuronal accumulation of phosphorylated neurofilaments. Acta Neuropathol (Berl) 72:369–376

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neurology, Fourth Department of Internal Medicine, Aichi Medical University, 480-11, Nagakute, Aichi, Japan

    G. Sobue & T. Mitsuma

  2. Department of Pathology, Nagoya University, School of Medicine, Nagoya, Japan

    Y. Hashizume

  3. Department of Neurology, Nagoya University, School of Medicine, Nagoya, Japan

    T. Yasuda

  4. Department of Neurology, National Nagoya Hospital, Nagoya, Japan

    E. Mukai

  5. Department of Child Neurology, Aichi Prefectural Colony Hospital, Nagoya, Japan

    T. Kumagai

  6. Department of Pathology and Laboratory Medicine, University of Pennsylvania, School of Medicine, Philadelphia, USA

    J. Q. Trojanowski

Authors
  1. G. Sobue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Hashizume
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Yasuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Mukai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Kumagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. Mitsuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Q. Trojanowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by grants from the Japanese Ministry of Health and Welfare, and the National Center for Nervous and Mental Health (NCNMH) of Japan

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sobue, G., Hashizume, Y., Yasuda, T. et al. Phosphorylated high molecular weight neurofilament protein in lower motor neurons in amyotrophic lateral sclerosis and other neurodegenerative diseases involving ventral horn cells. Acta Neuropathol 79, 402–408 (1990). https://doi.org/10.1007/BF00308716

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00308716

Key words

Search

Navigation