Skip to main content

Advertisement

SpringerLink
Log in

Transferrin localizes in Bunina bodies in amyotrophic lateral sclerosis

  • Original Article
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Transferrin, an iron-binding protein, plays an important role in the transport and delivery of circulating ferric iron to the tissues. Amyotrophic lateral sclerosis (ALS) is characterized by the presence of Bunina bodies, skein-like inclusions, Lewy body-like inclusions/round inclusions, and basophilic inclusions in the remaining anterior horn cells in the spinal cord. We examined transverse paraffin sections of lumbar spinal cords from 12 ALS cases including two ALS with dementia and two ALS with basophilic inclusions, using antibodies to human transferrin. The results demonstrated that transferrin localized in Bunina bodies and some of the basophilic inclusions. In contrast, skein-like inclusions and Lewy body-like inclusions or round inclusions did not show obviously detectable transferrin immunoreactivities. Our findings suggest that although the mechanisms underlying transferrin accumulation in Bunina bodies and basophilic inclusions are unknown, transferrin could be involved in forming these inclusions. Furthermore, following cystatin C, transferrin is the second protein that localizes in the Bunina bodies.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, Trojanowski JQ, Iwatsubo T (1998) Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am J Pathol 152:879–884

    PubMed  CAS  Google Scholar 

  2. Bloch B, Popovici T, Levin MJ, Tuil D, Kahn A (1985) Transferrin gene expression visualized in oligodendrocytes of the rat brain by using in situ hybridization and immunohistochemistry. Proc Natl Acad Sci USA 82:6706–6710

    Article  PubMed  CAS  Google Scholar 

  3. Fishman JB, Rubin JB, Handrahan JV, Connor JR, Fine RE (1987) Receptor-mediated transcytosis of transferrin across the blood–brain barrier. J Neurosci Res 18:299–304

    Article  PubMed  CAS  Google Scholar 

  4. Fujita Y, Okamoto K, Sakurai A, Kusaka H, Aizawa H, Mihara B, Gonatas NK (2002) The Golgi apparatus is fragmented in spinal cord motor neurons of amyotrophic lateral sclerosis with basophilic inclusions. Acta Neuropathol (Berl) 103:243–247

    Article  CAS  Google Scholar 

  5. Hart MN, Cancilla PA, Frommes S, Hirano A (1977) Anterior horn cell degeneration and Bunina-type inclusions associated with dementia. Acta Neuropathol (Berl) 38:225–228

    Article  CAS  Google Scholar 

  6. Kato T, Katagiri T, Hirano A, Kawanami T, Sasaki H (1989) Lewy body-like hyaline inclusions in sporadic motor neuron disease are ubiquitinated. Acta Neuropathol (Berl) 77:391–396

    Article  CAS  Google Scholar 

  7. Kato S, Saito M, Hirano A, Ohama E (1999) Recent advances in research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutations: neuronal Lewy body-like hyaline inclusions and astrocytic hyaline inclusions. Histol Histopathol 14:973–989

    PubMed  CAS  Google Scholar 

  8. Kuusisto E, Salminen A, Alafuzoff I (2002) Early accumulation of p62 in neurofibrillary tangles in Alzheimer’s disease: possible role in tangle formation. Neuropathol Appl Neurobiol 28:228–237

    Article  PubMed  CAS  Google Scholar 

  9. Leigh PN, Anderton BH, Dodson A, Gallo JM, Swash M, Power DM (1988) Ubiquitin deposits in anterior horn cells in motor neuron disease. Neurosci Lett 93:197–203

    Article  PubMed  CAS  Google Scholar 

  10. Levenson CW, Tassabehji NM (2004) Iron and ageing: an introduction to iron regulatory mechanisms. Ageing Res Rev 3:251–263

    Article  PubMed  CAS  Google Scholar 

  11. Liu HM, Atack JR, Rapoport SI (1989) Immunohistochemical localization of intracellular plasma proteins in the human central nervous system. Acta Neuropathol (Berl) 78:16–21

    Article  CAS  Google Scholar 

  12. Matsumoto S, Kusaka H, Ito H, Shibata N, Asayama T, Imai T (1996) Sporadic amyotrophic lateral sclerosis with dementia and Cu/Zn superoxide dismutase-positive Lewy body-like inclusions. Clin Neuropathol 15:41–46

    PubMed  CAS  Google Scholar 

  13. Mizuno Y, Amari M, Takatama M, Aizawa H, Mihara B, Okamoto K (2006) Immunoreactivities of p62, a ubiqutin-binding protein, in the spinal anterior horn cells of patients with amyotrophic lateral sclerosis. J Neurol Sci (in press)

  14. Mizusawa H, Hirano A, Yen SHC (1991) Anterior horn cell inclusions in familial amyotrophic lateral sclerosis contain ubiqutin and phosphorylated neurofilament epitopes. Neuropathology 11:11–20

    Google Scholar 

  15. Moos T (1995) Age-dependent uptake and retrograde axonal transport of exogenous albumin and transferrin in rat motor neurons. Brain Res 672:14–23

    Article  PubMed  CAS  Google Scholar 

  16. Morris CM, Candy JM, Bloxham CA, Edwardson JA (1992) Immunocytochemical localisation of transferrin in the human brain. Acta Anat (Basel) 143:14–18

    CAS  Google Scholar 

  17. Nagai A, Murakawa Y, Terashima M, Shimode K, Umegae N, Takeuchi H, Kobayashi S (2000) Cystatin C and cathepsin B in CSF from patients with inflammatory neurologic diseases. Neurology 55:1828–1832

    PubMed  CAS  Google Scholar 

  18. Nagai A, Terashima M, Harada T, Shimode K, Takeuchi H, Murakawa Y, Nagasaki M, Nakano A, Kobayashi S (2003) Cathepsin B and H activities and cystatin C concentrations in cerebrospinal fluid from patients with leptomeningeal metastasis. Clin Chim Acta 329:53–60

    Article  PubMed  CAS  Google Scholar 

  19. Nakano I, Hashizume Y, Tomonaga T (1990) Bunina bodies in neurons of the medullary reticular formation in a case of amyotrophic lateral sclerosis. Acta Neuropathol (Berl) 79:689–691

    Article  CAS  Google Scholar 

  20. Nakano T, Nakaso K, Nakashima K, Ohama E (2004) Expression of ubiquitin-binding protein p62 in ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis with dementia: analysis of five autopsy cases with broad clinicopathological spectrum. Acta Neuropathol (Berl) 107:359–364

    Article  CAS  Google Scholar 

  21. Okamoto K (1993) Bunina bodies in amyotrophic lateral sclerosis. Neuropathology 13:193–199

    Google Scholar 

  22. Okamoto K, Morimatsu M, Hirai S, Ishida Y (1980) Intracytoplasmic inclusions (Bunina bodies) in amyotrophic lateral sclerosis. Acta Pathol Jpn 30:591–597

    PubMed  CAS  Google Scholar 

  23. Okamoto K, Hirai S, Amari M, Watanabe M, Sakurai A (1993) Bunina bodies in amyotrophic lateral sclerosis immunostained with rabbit anti-cystatin C serum. Neurosci Lett 162:125–128

    Article  PubMed  CAS  Google Scholar 

  24. Piubelli C, Fiorini M, Zanusso G, Milli A, Fasoli E, Monaco S, Righetti PG (2006) Searching for markers of Creutzfeldt–Jakob disease in cerebrospinal fluid by two-dimensional mapping. Proteomics 6:S256–S261

    Article  PubMed  Google Scholar 

  25. Reed CH (2000) Diagnostic applications of cystatin C. Br J Biomed Sci 57:323–329

    Article  PubMed  CAS  Google Scholar 

  26. Sparrow JR (1981) Immunocytochemical localization of plasma proteins in neuronal perikarya. Brain Res 212:159–163

    Article  PubMed  CAS  Google Scholar 

  27. Stumptner C, Heid H, Fuchsbichler A, Hauser H, Mischinger HJ, Zatloukal K, Denk H (1999) Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent. Am J Pathol 154:1701–1710

    PubMed  CAS  Google Scholar 

  28. Vannier-Santos MA, Martiny A, Lins U, Urbina JA, Borges VM, de Souza W (1999) Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes. Microbiology 145:3213–3220

    PubMed  CAS  Google Scholar 

  29. Yu HL, Chertkow HM, Bergman H, Schipper HM (2003) Aberrant profiles of native and oxidized glycoproteins in Alzheimer plasma. Proteomics 3:2240–2248

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Ministry of Health, Labor and Welfare of Japan to K. Okamoto.

Author information

Authors and Affiliations

  1. Department of Neurology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Yuji Mizuno & Koichi Okamoto

  2. Department of Internal Medicine, Geriatrics Research Institute and Hospital, 3-26-8 Otomo-machi, Maebashi, Gunma, 371-0847, Japan

    Masakuni Amari & Masamitsu Takatama

  3. First Department of Internal Medicine, Asahikawa Medical College, Asahikawa, 078-8510, Japan

    Hitoshi Aizawa

  4. Institute of Brain and Blood Vessels, Mihara Memorial Hospital, 366 Ota-machi, Isesaki, Gunma, 372-0006, Japan

    Ban Mihara

Authors
  1. Yuji Mizuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masakuni Amari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masamitsu Takatama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hitoshi Aizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ban Mihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Koichi Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuji Mizuno.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mizuno, Y., Amari, M., Takatama, M. et al. Transferrin localizes in Bunina bodies in amyotrophic lateral sclerosis. Acta Neuropathol 112, 597–603 (2006). https://doi.org/10.1007/s00401-006-0122-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-006-0122-4

Keywords

Search

Navigation