Neuronal Intranuclear Inclusions in Neostriatal Striosomes and Matrix in Huntington’s Disease

  • John C. Hedreen
Part of the Advances in Behavioral Biology book series (ABBI, volume 54)

Abstract

Neuronal intranuclear inclusions have recently been described in the cerebral cortex and neostriatum in Huntington’s disease brain that are demonstrable immunocytochemically with antibodies to N-terminal huntingtin and to ubiquitin. Their distribution by region and by neuron type matches the known vulnerability pattern in Huntington’s disease, and it is thought that the presence of inclusions is a marker for future cell degeneration. We recently described a preferential loss of medium spiny neurons in neostriatal striosomes relative to the matrix, as defined by calbindin immunostaining, in early to middle stages of Huntington’s disease. We now show that ubiquitinated neuronal intranuclear inclusions are present in a greater proportion of the medium spiny neurons of striosomes than in those of the matrix in Huntington’s disease brains (Vonsattel grade 0–3). The proportion in striosomes correlates strongly with age at death, probably a reflection of CAG repeat length, whereas in the matrix the proportion with inclusions correlates with Vonsattel grade. The fmding of a preferential involvement of striosomal medium spiny neurons early in the course of disease is consistent both with the hypothesis of greater vulnerability of striosomal neurons to the pathogenic process in Huntington’s disease, and with the idea that the inclusions are harbingers of cell death.

Keywords

Glutamine Neurol Paraffin Polyglutamine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    DiFiglia, M., Sapp, E., Chase, K.O., Davies, S.W., Bates, G.P., Vonsattel, J.P., and Aronin, N., 1997, Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain.Science277:1990–1993.PubMedCrossRefGoogle Scholar
  2. 2.
    Becher, M.W., Kotzuk, J.A., Sharp, A.H., Davies, S.W., Price, D.L., and Ross, C.A., 1998, Intranuclear neuronal inclusions in Huntington’s disease and dentatorubral and pallidoluysian atrophy: correlation between the density of inclusions and IT15 triplet repeat length.Neurobiol. Dis.4:387–397.PubMedCrossRefGoogle Scholar
  3. 3.
    Hedreen, J.C., and Folstein, S.E., 1995, Early loss of neostriatal striosome neurons in Huntington’s disease.J. Neuropath. Exp. Neurol.54:105–120.PubMedCrossRefGoogle Scholar
  4. 4.
    Augood, S.J., Fault, R.L., Love, D.R., and Emson, P.C., 1996, Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington’s disease: a detailed cellularin situhybridization study.Neurosci.72:1023–1036.CrossRefGoogle Scholar
  5. 5.
    Ross, C.A., 1997, Intranuclear neuronal inclusions: A common pathogenic mechanism for glutaminerepeat neurodegenerative diseases?Neuron19:1147–1150.PubMedCrossRefGoogle Scholar
  6. 6.
    Paulson, H.L., 1999, Protein fate in neurodegenerative proteinopathies: polyglutamine diseases join the (mis)fold.Am. J. Hum. Genet.64:339–345.PubMedCrossRefGoogle Scholar
  7. 7.
    Vonsattel, J.P., Myers, R.H., Stevens, T.J., Ferrante, R.J., Bird, E.D., and Richardson, E.P. Jr., 1985, Neuropathological classification of Huntington’s disease.J. Neuropath. Exp. Neural.44:559–577.CrossRefGoogle Scholar
  8. 8.
    Hedreen, J.C., and Mucci, L.A., 1995, Antigen retrieval for paraffin section immunohistochemistry with antibodies commonly used in studies of degenerative diseases.Soc. Neurosci. Abstr.21:1802.Google Scholar
  9. 9.
    Gusella, J.F., and MacDonald, M.E., 1995, Huntington’s disease: CAG genetics expands neurobiology.Curr. Opin. Neurobiol.5:656–662.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • John C. Hedreen
    • 1
  1. 1.Dept. of PsychiatryNew England Medical CenterBostonUSA

Personalised recommendations