Skip to main content
Log in

Immunohistochemical identification of messenger RNA-related proteins in basophilic inclusions of adult-onset atypical motor neuron disease

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

Abstract

This report concerns an immunohistochemical investigation on RNA-related proteins in the basophilic inclusions (BIs) from patients with adult-onset atypical motor neuron disease. Formalin-fixed, paraffin-embedded sections of the motor cortex and the lumbar spinal cord were examined. The BIs appeared blue in color with H&E and Nissl stain, and pink with methylgreen–pyronin stain. Ribonuclease pretreatment abolished the methylgreen–pyronin staining, suggesting that the BIs contained RNA. Immunohistochemically, the BIs were distinctly labeled with the antibodies against poly(A)-binding protein 1, T cell intracellular antigen 1, and ribosomal protein S6. These proteins are essential constituents of stress granules. In contrast, the BIs were not immunoreactive for ribosomal protein L28 and decapping enzyme 1, which are core components of transport ribonucleoprotein particles and processing bodies, respectively. Moreover, the BIs were not immunopositive for TDP-43. Our results imply that translation attenuation could be involved in the processes of BI formation in this disorder.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Anderson P, Kedersha N (2002) Stressful initiations. J Cell Sci 115:3227–3234

    PubMed  CAS  Google Scholar 

  2. Anderson P, Kedersha N (2006) RNA granules. J Cell Biol 172:803–808

    Article  PubMed  CAS  Google Scholar 

  3. Andrei MA, Ingelfinger D, Heintzmann R, Achsel T, Rivera-Pomar R, Lührmann R (2005) A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies. RNA 11:717–727

    Article  PubMed  CAS  Google Scholar 

  4. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y, Oda T (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351:602–611

    Article  PubMed  CAS  Google Scholar 

  5. Bramham CR, Wells DG (2007) Dendric mRNA: transport, translation and function. Nat Rev Neurosci 8:776–789

    Article  PubMed  CAS  Google Scholar 

  6. Brooks BR, Miller RG, Swash M, Munsat TL, World Federation of Neurology Research Group on Motor Neuron Diseases (2000) El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–299

    Article  PubMed  CAS  Google Scholar 

  7. Buratti E, Dörk T, Zuccato E, Pagani F, Romano M, Baralle FE (2001) Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J 20:1774–1784

    Article  PubMed  CAS  Google Scholar 

  8. Buratti E, Baralle FE (2001) Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9. J Biol Chem 276:36337–36343

    Article  PubMed  CAS  Google Scholar 

  9. Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DM, Consortium for frontotemporal lobar degeneration (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathol (Berl) 114:5–22

    Article  Google Scholar 

  10. Hamada K, Fukazawa T, Yanagihara T, Yoshida K, Hamada T, Yoshimura N, Tashiro K (1995) Dementia with ALS features and diffuse Pick body-like inclusions (atypical Pick’s disease?). Clin Neuropathol 14:1–6

    PubMed  CAS  Google Scholar 

  11. Hirano A, Iwata M (1979) Pathology of motor neurons with special reference to amyotrophic lateral sclerosis and related disease. In: Tsubaki T, Toyokura Y (eds) Amyotrophic lateral sclerosis. University of Tokyo Press, Tokyo, pp 107–133

    Google Scholar 

  12. Ishihara K, Araki S, Ihori N, Shiota J, Kawamura M, Nakano I (2006) An autopsy case of frontotemporal dementia with severe dysarthria and motor neuron disease showing numerous basophilic inclusions. Neuropathology 26:447–454

    Article  PubMed  Google Scholar 

  13. Ivanov PA, Nadezhdina ES (2006) Stress granules: RNP-containing cytoplasmic bodies arising in stress: structure and mechanism of organization. Mol Biol 40:844–850

    Article  CAS  Google Scholar 

  14. Kedersha NL, Gupta M, Li W, Miller I, Anderson P (1999) RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. J Cell Biol 147:1431–1442

    Article  PubMed  CAS  Google Scholar 

  15. Kedersha N, Cho MR, Li W, Yacono PW, Chen S, Gilks N, Golan DE, Anderson P (2000) Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules. J Cell Biol 151:1257–1268

    Article  PubMed  CAS  Google Scholar 

  16. Kiebler MA, Bassell GL (2006) Neuronal RNA granules: movers and makers. Neuron 51:685–690

    Article  PubMed  CAS  Google Scholar 

  17. Krichevsky AM, Kosik KS (2001) Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation. Neuron 32:683–696

    Article  PubMed  CAS  Google Scholar 

  18. Kusaka H, Matsumoto S, Imai T (1990) An adult-onset case of sporadic motor neuron disease with basophilic inclusions. Acta Neuropathol (Berl) 80:660–665

    Article  CAS  Google Scholar 

  19. Kusaka H, Matsumoto S, Imai T (1993) Adult-onset motor neuron disease with basophilic intraneuronal inclusion bodies. Clin Neuropathol 12:215–218

    PubMed  CAS  Google Scholar 

  20. Mangus DA, Evans MC, Jacobson A (2003) Poly(A)-binding proteins: multi-functional scaffolds for the post-transcriptional control of gene expression. Genome Biol 4:223–236

    Article  PubMed  Google Scholar 

  21. Mizuno Y, Amari M, Takatama M, Aizawa H, Mihara B, Okamoto K (2006) Transferrin localizes in Bunina bodies in amyotrophic lateral sclerosis. Acta Neuropathol 112:597–603

    Article  PubMed  CAS  Google Scholar 

  22. Munoz-Garcia D, Ludwin SK (1988) Classic and generalized variants of Pick’s disease: a clinicopathological, ultrastructual, and immunocytochemical comparative study. Ann Neurol 16:467–480

    Article  Google Scholar 

  23. Munoz DG (1998) The pathology of pick complex. In: Munoz DG (ed) Pick’s disease and pick complex. Wiley, New York, pp 211–241

    Google Scholar 

  24. Murayama S, Mori H, Ihara Y, Bouldin TW, Suzuki K, Tomonaga M (1990) Immunocytochemical and ultrastructural studies of lower motor neurons in amyotrophic lateral sclerosis. Ann Neurol 27:137–148

    Article  PubMed  CAS  Google Scholar 

  25. Nakano S, Shinde A, Ito H, Ito H, Kusaka H (2005) Messenger RNA degradation may be inhibited in sporadic inclusion body myositis. Neurology 65:420–425

    Article  PubMed  CAS  Google Scholar 

  26. Nelson JS, Prensky AL (1972) Sporadic juvenile amyotrophic lateral sclerosis. a clinic-pathological study of a case with neuronal cytoplasmic inclusions containing RNA. Arch Neurol 27:300–306

    PubMed  CAS  Google Scholar 

  27. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133

    Article  PubMed  CAS  Google Scholar 

  28. Oda M, Akagawa N, Tabuchi Y, Tanabe H (1978) A sporadic juvenile case of the amyotrophic lateral sclerosis with neuronal intracytoplasmic inclusions. Acta Neuropathol (Berl) 44:211–216

    Article  CAS  Google Scholar 

  29. Okamoto K, Hirai S, Yamazaki T, Sun XY, Nakazato Y (1991) New ubiquitin-positive intraneuronal inclusions in the extra-motor cortices in patients with amyotrophic lateral sclerosis. Neurosci Lett 129:233–236

    Article  PubMed  CAS  Google Scholar 

  30. Parker R, Sheth U (2007) P bodies and the control of mRNA translation and degradation. Mol Cell 25:635–646

    Article  PubMed  CAS  Google Scholar 

  31. Sasaki S, Toi S, Shirata A, Yamane K, Sakuma H, Iwata M (2001) Immunohistochemical and ultrastructual study of basophilic inclusions in adult-onset motor neuron disease. Acta Neuropathol (Berl) 102:200–206

    CAS  Google Scholar 

  32. Wang IF, Wu LS, Chang HY, Shen CK (2008) TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor. J Neurochem 105:797–806

    Article  PubMed  CAS  Google Scholar 

  33. Yokota O, Tsuchiya K, Terada S, Ishizu H, Uchikado H, Ikeda M, Oyanagi K, Nakano I, Murayama S, Kuroda S, Akiyama H (2008) Basophilic inclusion body disease and neuronal intermediate filament inclusion disease: a comparative clinicopathological study. Acta Neuropathol 115:561–575

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

We express our sincere appreciation to Miss Tomoko Takemi for her technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hidefumi Ito.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fujita, K., Ito, H., Nakano, S. et al. Immunohistochemical identification of messenger RNA-related proteins in basophilic inclusions of adult-onset atypical motor neuron disease. Acta Neuropathol 116, 439–445 (2008). https://doi.org/10.1007/s00401-008-0415-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-008-0415-x

Keywords

Navigation