The Golgi apparatus is fragmented in spinal cord motor neurons of amyotrophic lateral sclerosis with basophilic inclusions

• Published in: Acta neuropathologica 2002-03, Vol.103 (3), p.243-247
• Main Authors: FUJITA, Yukio, OKAMOTO, Koichi, SAKURAI, Atsushi, KUSAKA, Hirofumi, AIZAWA, Hitoshi, MIHARA, Ban, GONATAS, Nicholas K
• Format: Article
• Language: English
• Subjects: Adult; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - immunology; Amyotrophic Lateral Sclerosis - pathology; Anterior Horn Cells - immunology; Anterior Horn Cells - pathology; Antibodies; Basophils - immunology; Basophils - pathology; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Fragmentation - genetics; DNA Fragmentation - immunology; Female; Golgi Apparatus - genetics; Golgi Apparatus - immunology; Golgi Apparatus - pathology; Humans; Inclusion Bodies - immunology; Inclusion Bodies - pathology; Male; Medical sciences; Medicine; Middle Aged; Motor neurone disease; Motor Neurons - immunology; Motor Neurons - pathology; Mutation; Mutation - genetics; Mutation - immunology; Neurology; Patients; Spinal cord; Spinal Cord - immunology; Spinal Cord - pathology; Superoxide Dismutase - genetics; Superoxide Dismutase - immunology; Superoxide Dismutase-1; Transgenic animals
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s004010100461

The mechanisms of neuronal death in amyotrophic lateral sclerosis (ALS) are not known. A pathological aggregation of cytoplasmic constituents in the form of variety of inclusions may play a role in the pathogenesis of neuronal death. Cytoplasmic basophilic inclusions (BIs) in motor neurons are commonly found in sporadic juvenile ALS. The functional significance of these inclusions is not known, i.e., whether they represent a protective reaction for the isolation of abnormal products from the cytoplasm, or a sign of irreversible neuronal damage. To gain insights on the significance of BIs we asked whether neurons with BIs had an intact or fragmented Golgi apparatus (GA), a sign of neuronal degeneration reported not only in sporadic and familial ALS with mutations of the Cu/Zn superoxide dismutase gene (SOD1), but also in transgenic mice expressing the G93A mutation of SOD1. In these mice fragmentation of the GA of spinal cord motor neurons was found months before the onset of paralysis. We report here that all neurons bearing the inclusions showed fragmentation and reduced number of GA. These results suggest that common pathogenetic mechanisms are involved in the production of BIs and in the fragmentation of the GA.