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Involvement of Onuf’s nucleus in Machado–Joseph disease: a morphometric and immunohistochemical study

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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.

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Acknowledgments

We thank C. Tanda, J. Takasaki, H. Saito, T. Fujita, and S. Egawa for their technical assistance, and M. Machida and Y. Ueda for secretarial assistance. This work was supported by a grant from the Research Committee for Ataxic Diseases, the Ministry of Health, Labour and Welfare, Japan (to M.Y.); a research grant (19A-4) for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare, Japan (to M.Y.); Grants-in-Aid 20500322 (to Y.T.); and 20240037 (to H.T.) for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and a Project Research Promotion Grant from the University of Niigata (to H.T.).

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  1. Mitsunori Yamada

    Present address: Department of Clinical Research, National Hospital Organization, Saigata National Hospital, Joetsu, 949-3193, Japan

Authors and Affiliations

  1. Department of Pathology, Brain Research Institute, University of Niigata, 1-757 Asahimachi, Chuo-ku, Niigata, 951-8585, Japan

    Hiroshi Shimizu, Mitsunori Yamada, Yasuko Toyoshima & Hitoshi Takahashi

  2. Department of Molecular Neuroscience, Center for Bioresources, Brain Research Institute, University of Niigata, Niigata, 951-8585, Japan

    Takeshi Ikeuchi & Osamu Onodera

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  1. Hiroshi Shimizu
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Correspondence to Hitoshi Takahashi.

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Shimizu, H., Yamada, M., Toyoshima, Y. et al. Involvement of Onuf’s nucleus in Machado–Joseph disease: a morphometric and immunohistochemical study. Acta Neuropathol 120, 439–448 (2010). https://doi.org/10.1007/s00401-010-0699-5

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  • DOI: https://doi.org/10.1007/s00401-010-0699-5

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