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

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 73; no. 4; pp. 450 - 452
• Main Authors: Koyano, S, Iwabuchi, K, Yagishita, S, Kuroiwa, Y, Uchihara, T
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.10.2002; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Antibodies, Anti-Idiotypic - immunology; Apoptosis; Ataxia; Biological and medical sciences; CAG/polyglutamine; Cell Death; Cerebellar ataxia; Cerebellum - immunology; Cerebellum - pathology; Culture Techniques; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dentatorubal pallidoluysian atrophy; DRPLA; Expansion; Genetic aspects; Golgi Apparatus - metabolism; Golgi Apparatus - pathology; hereditary ataxias; Humans; Huntingtons disease; Immunohistochemistry; Inclusion Bodies - immunology; Inclusion Bodies - pathology; Medical sciences; Neurodegeneration; Neurology; neuronal intranuclear inclusion; Neurons - immunology; Neurons - pathology; nuclear inclusion; Pathogenesis; Peptides - immunology; Physiological aspects; Purkinje; Purkinje cell; Purkinje cells; Purkinje Cells - immunology; Purkinje Cells - pathology; SBMA; Short Report; spinobulbar muscular atrophy; Spinocerebellar Degenerations - genetics; Spinocerebellar Degenerations - immunology; Spinocerebellar Degenerations - pathology; Trinucleotide Repeat Expansion - genetics; Human; Nervous system diseases; Pathogenesis; Cell nucleus; Trinucleotide; Purkinje neuron; Genetic determinism; Cerebral disorder; Genetic disease; Cerebellar disease; Spinocerebellar ataxia; Central nervous system disease; Cell inclusion; Degenerative disease; Dentatorubropallidoluysian atrophy; Expansion
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.73.4.450

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.