Schwann cell involvement in the peripheral neuropathy of spinocerebellar ataxia type 3

• Published in: Neuropathology and applied neurobiology Vol. 40; no. 5; pp. 628 - 639
• Main Authors: Suga, Noriaki, Katsuno, Masahisa, Koike, Haruki, Banno, Haruhiko, Suzuki, Keisuke, Hashizume, Atsushi, Mano, Tomoo, Iijima, Masahiro, Kawagashira, Yuichi, Hirayama, Masaaki, Nakamura, Tomohiko, Watanabe, Hirohisa, Tanaka, Fumiaki, Sobue, Gen
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.08.2014; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Ataxia; Ataxin-3; clinical neurophysiology; Female; Humans; immunohistochemistry; Machado-Joseph disease; Machado-Joseph Disease - pathology; Machado-Joseph Disease - physiopathology; Male; Medical research; Middle Aged; Nerve Tissue Proteins - metabolism; Nuclear Proteins - metabolism; Peripheral Nervous System Diseases - pathology; Peripheral Nervous System Diseases - physiopathology; peripheral neuropathy; polyglutamine; Repressor Proteins - metabolism; Schwann Cells - metabolism; Schwann Cells - pathology; spinocerebellar ataxia; Young Adult; Machado-Joseph disease; immunohistochemistry; clinical neurophysiology; polyglutamine; peripheral neuropathy; spinocerebellar ataxia
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1111/nan.12055

Aims Spinocerebellar ataxia type 3 (SCA3) is an inherited spinocerebellar ataxia caused by the expansion of trinucleotide CAG repeats in the gene encoding ataxin‐3. The clinical manifestations of SCA3 include peripheral neuropathy, which is an important cause of disability in a subset of patients. Although the loss of neurones in the dorsal root ganglion (DRG) has been postulated to be the cause of this neuropathy, the precise mechanism remains to be elucidated. Methods To clarify the clinicopathological characteristics of SCA3‐associated peripheral neuropathy, we performed nerve conduction studies and histopathological analyses. Nerve conduction studies were carried out in 18 SCA3 patients. Immunohistochemical analyses of the anterior and posterior roots of the spinal cord and peripheral nerves were performed in five SCA3 patients. We also employed immunohistochemistry and immunoelectron microscopy analyses with an anti‐polyglutamine antibody. Results The mean sensory nerve action potentials of the SCA3 patients were half of the normal values. The motor conduction velocities were decreased, and the distal latencies were also significantly prolonged in the nerves studied relative to the those in normal controls. Histopathological analyses detected axonal sprouting and myelin thinning in all cases. Ataxin‐3 aggregates were found in the cytoplasm of Schwann cells in all of the SCA3 patients examined but not in control subjects. Conclusions In addition to the previously reported neuronopathy, the results of the present study indicate that Schwann cells are involved in the formation of the pathogenic intracytoplasmic ataxin‐3 protein aggregates in patients with SCA3‐associated neuropathy.