Acta Neuropathologica

, Volume 96, Issue 6, pp 547–552

Hereditary dentatorubral-pallidoluysian atrophy: detection of widespread ubiquitinated neuronal and glial intranuclear inclusions in the brain

  • Yasuko Hayashi
  • Akiyoshi Kakita
  • Mitsunori Yamada
  • Reiji Koide
  • Shuichi Igarashi
  • Hiroki Takano
  • Takeshi Ikeuchi
  • Koichi Wakabayashi
  • Shigekimi Egawa
  • Shoji Tsuji
  • H. Takahashi
Regular paper

DOI: 10.1007/s004010050933

Cite this article as:
Hayashi, Y., Kakita, A., Yamada, M. et al. Acta Neuropathol (1998) 96: 547. doi:10.1007/s004010050933

Abstract

We examined the brains and spinal cords of seven patients with clinicopathologically and genetically confirmed hereditary dentatorubral-pallidoluysian atrophy (DRPLA) using an antibody against ubiquitin, and found small, round immunoreactive intranuclear inclusions in both neurons and glial cells in various brain regions. Ubiquitinated neuronal intranuclear inclusions (uNIIs) were consistently found in the striatum, the pontine nuclei, the inferior olivary complex, the cerebellar cortex and the dentate nucleus. Ubiquitinated glial intranuclear inclusions (uGIIs) were found less frequently than uNIIs. Most of the inclusion-bearing nuclei were of an astrocytic nature. Immunostaining with an antibody against DRPLA protein revealed similar immunoreactive neuronal and glial intranuclear inclusions, but in much smaller in numbers compared with uNIIs and uGIIs. Electron microscopy showed that such inclusions were composed of granular and filamentous structures. These findings strongly suggest that, in DRPLA, the occurrence of uNIIs and uGIIs is directly related to the causative gene abnormality (an expanded CAG repeat encoding polyglutamine), that neurons are affected much more widely than previously recognized and that glial cells are also involved in the disease process.

Key words Dentatorubral-pallidoluysian atrophyNuclear inclusionUbiquitinImmunohistochemistryUltrastructure

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Yasuko Hayashi
    • 1
  • Akiyoshi Kakita
    • 1
  • Mitsunori Yamada
    • 1
  • Reiji Koide
    • 2
  • Shuichi Igarashi
    • 2
  • Hiroki Takano
    • 2
  • Takeshi Ikeuchi
    • 2
  • Koichi Wakabayashi
    • 3
  • Shigekimi Egawa
    • 1
  • Shoji Tsuji
    • 2
  • H. Takahashi
    • 1
  1. 1.Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata 951-8585, Japan e-mail: hitoshi@bri.niigata-u.ac.jp, Tel.: +81-25-227-0633, Fax: +81-25-227-0817JP
  2. 2.Department of Neurology, Brain Research Institute, Niigata University, Niigata, JapanJP
  3. 3.Brain Disease Research Center, Brain Research Institute, Niigata University, Niigata, JapanJP