Abstract

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.