Paradoxical absence of nuclear inclusion in cerebellar Purkinje cells of hereditary ataxias linked to CAG expansion

J Neurol Neurosurg Psychiatry. 2002 Oct;73(4):450-2. doi: 10.1136/jnnp.73.4.450.

Abstract

Degeneration of cerebellar cortex is one of the principal features of hereditary ataxias linked to expansion of CAG repeat. In an attempt to clarify possible correlation between neuronal depletion and neuronal intranuclear inclusions, both triggered by the pathological expansion of CAG repeat, cerebellar sections from SCA1, SCA2, SCA3, and DRPLA cases were immunostained with anti-ubiquitin or anti-expanded polyglutamine antibody (1C2) and were screened for the presence of neuronal intranuclear inclusions. Although the degree of cerebellar degeneration varied greatly, cerebellar Purkinje cells were uniformly characterised by the absence of neuronal intranuclear inclusion. Complete absence of neuronal intranuclear inclusion in Purkinje cells is apparently paradoxical and hardly explained if neuronal intranuclear inclusion formation is positively correlated to a mechanism accelerating neuronal death. It may, otherwise, suggest an intrinsic link between neuronal intranuclear inclusion formation and neurodegeneration in opposite directions in human Purkinje cells, more or less affected in these CAG repeat disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Anti-Idiotypic / immunology
  • Cell Death
  • Cerebellum / immunology
  • Cerebellum / pathology*
  • Culture Techniques
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / pathology
  • Humans
  • Immunohistochemistry
  • Inclusion Bodies / immunology
  • Inclusion Bodies / pathology*
  • Neurons / immunology
  • Neurons / pathology
  • Peptides / immunology
  • Purkinje Cells / immunology
  • Purkinje Cells / pathology*
  • Spinocerebellar Degenerations / genetics*
  • Spinocerebellar Degenerations / immunology
  • Spinocerebellar Degenerations / pathology*
  • Trinucleotide Repeat Expansion / genetics*

Substances

  • Antibodies, Anti-Idiotypic
  • Peptides
  • polyglutamine