title: Involvement of Onuf's nucleus in Machado-Joseph disease: a morphometric and immunohistochemical study.
abstract: Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disease caused by an expansion of CAG repeats in the MJD1 gene, in which lower urinary tract dysfunction is known to be the most commonly encountered autonomic failure. However, it remains unclear whether Onuf's nucleus (ON), which plays major roles in the micturition reflex and voluntary continence, degenerates during the disease process. In the present study, we conducted a morphometric and immunohistochemical study of ON, together with the lateral nuclear group (LNG) of the sacral anterior horns, in seven patients with MJD. When compared with controls, the number of lower motor neurons in both ON and LNG was significantly smaller in the MJD patients, the former being inversely correlated with the size of the expanded CAG repeats. Notably, MJD patients with a large CAG-repeat expansion showed an ON-predominant pattern of neuronal loss, while in the remaining patients, ON and LNG were affected to a similar degree, or rather an LNG-predominant pattern of neuronal loss was evident. Moreover, when adjusted for age, the degree of neuronal loss in both ON and LNG was significantly correlated with the extent of expansion of the CAG repeats. In MJD, the remaining lower motor neurons in ON often exhibited ataxin-3- or 1C2-immunoreactive (ir) neuronal intranuclear inclusions, while no pTDP-43-ir neuronal cytoplasmic inclusions were present in these neurons. In conclusion, the present findings strongly suggest that neuronal loss in ON, the degree of which is highly influenced by the extent of expansion of CAG repeats, is a consistent feature in MJD.
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Chuo-ku, Niigata 951-8585, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Yamada
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ikeuchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000067699:Ataxin-3; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D017827:Machado-Joseph Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000145:classification / Q000473:pathology / Q000648:ultrastructure*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology*; D018709:Statistics, Nonparametric; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism; D014549:Urinary Incontinence / Q000209:etiology
chemical_list: D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D025801:Ubiquitin; C092341:ATXN3 protein, human; D000067699:Ataxin-3