Attenuated nuclear shrinkage in neurones with nuclear inclusions of SCA1 brains
- 1Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
- 2Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience
- 3Department of Pathology, Tokyo Metropolitan Komagome Hospital
- 4Department of Neurology and Psychiatry, Kanagawa Rehabilitation Centre, Atsugi, Japan
- 5Department of Pathology, Kanagawa Rehabilitation Centre
- 6Department of Neurology, National Sanatorium Nishitaga Hospital, Miyagi, Japan
- 7Department of Neurology, Miyagi National Hospital
- 8Third Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan
- Correspondence to: Dr T Uchihara, Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan;
- Received 20 June 2002
- Accepted 21 November 2002
- Revised 12 November 2002
Background: Spinocerebellar ataxia type 1 (SCA1) is one of the autosomal dominant neurodegenerative disorders commonly linked to pathological expansion of the CAG repeat of the relevant gene. Nuclear inclusions and neurodegeneration are both triggered by this pathological expansion of the CAG/polyglutamine repeat on ataxin-1, but it remains to be determined whether or not nuclear inclusion formation is associated with accelerated neurodegeneration.
Objective: To examine the influence of nuclear inclusions on nuclear size and deformity in human brains from patients suffering from SCA1.
Material: Pontine sections of brains obtained at necropsy from seven patients with SCA1 and five controls.
Methods: The size and deformity of each neuronal nucleus was quantified. Nuclei with and without inclusions were examined separately to assess the possible influence of nuclear inclusions on neurodegeneration.
Results: Nuclear shrinkage and deformity were more marked in SCA1 brains than in controls. This shrinkage was attenuated in neurones containing nuclear inclusions.
Conclusions: The existence of nuclear inclusions in SCA1 is presumably linked to a mechanism that attenuates rather than accelerates nuclear shrinkage. This in vivo finding may provide a clue to constructing a rational therapeutic strategy for combating neurodegeneration associated with nuclear inclusions.
- CI, circularity index
- DRPLA, dentatorubral-pallidoluysian atrophy
- NIHID, neuronal intranuclear hyaline inclusion disease
- NI+, nuclear inclusions present
- NI−, nuclear inclusions absent
- SCA1, spinocerebellar ataxia type 1
Competing interests: none declared