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Pathoanatomy of Cerebellar Degeneration in Spinocerebellar Ataxia Type 2 (SCA2) and Type 3 (SCA3)

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Abstract

The cerebellum is one of the well-known targets of the pathological processes underlying spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3). Despite its pivotal role for the clinical pictures of these polyglutamine ataxias, no pathoanatomical studies of serial tissue sections through the cerebellum have been performed in SCA2 and SCA3 so far. Detailed pathoanatomical data are an important prerequisite for the identification of the initial events of the underlying disease processes of SCA2 and SCA3 and the reconstruction of its spread through the brain. In the present study, we performed a pathoanatomical investigation of serial thick tissue sections through the cerebellum of clinically diagnosed and genetically confirmed SCA2 and SCA3 patients. This study demonstrates that the cerebellar Purkinje cell layer and all four deep cerebellar nuclei consistently undergo considerable neuronal loss in SCA2 and SCA3. These cerebellar findings contribute substantially to the pathogenesis of clinical symptoms (i.e., dysarthria, intention tremor, oculomotor dysfunctions) of SCA2 and SCA3 patients and may facilitate the identification of the initial pathological alterations of the pathological processes of SCA2 and SCA3 and reconstruction of its spread through the brain.

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Notes

  1. Please note that these oculomotor dysfunctions evolve during different disease stages of SCA2 and SCA3. They may change their clinical features or even disappear in the advanced disease stages of SCA2 and SCA3 reflecting the widespread affection, but different vulnerability of the structures of the oculomotor network of the human brain and the chronological sequence of their affection during SCA2 and SCA3.

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Acknowledgments

This study was supported by grants from the Deutsche Forschungsgemeinschaft (RU 1215/1-2), the Deutsche Heredo-Ataxie Gesellschaft (DHAG), the ADCA-Vereniging Nederland, the Stiftung Hofffnung (Köln, Germany) and the Dr. Senckenbergische Stiftung (Frankfurt/Main, Germany). The skillful assistance of M. Babl, B. Meseck-Selchow, M. Bouzrou (tissue processing and immunohistochemistry), I. Szasz (graphics), M. Hütten and D. von Meltzer (secretary) is thankfully acknowledged.

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Authors and Affiliations

  1. Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany

    W. Scherzed, K. Seidel, D. Del Turco, T. Deller & U. Rüb

  2. Department of Neurology, University Medical Center Groningen, University of Groningen, NL-5970 RB, Groningen, The Netherlands

    E. R. Brunt

  3. Morphological Brain Research Unit, Julius Maximilians University, 97080, Würzburg, Germany

    H. Heinsen

  4. Laboratorium Pathologie Oost Nederland, NL-7512 AD, Enschede, The Netherlands

    R. A. de Vos

  5. Institute of Cell Biology, Department of Immunology, University of Tübingen, 72076, Tübingen, Germany

    K. Bürk

  6. Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, 72076, Tübingen, Germany

    L. Schöls

  7. German Center of Neurodegenerative Diseases (DZNE), University of Tübingen, 72076, Tübingen, Germany

    L. Schöls

  8. Molecular Neurogenetics, Department of Neurology, Goethe-University, 60590, Frankfurt/Main, Germany

    G. Auburger

  9. Dr. Senckenberg Chronomedical Institute, Goethe-University, 60590, Frankfurt/Main, Germany

    H. W. Korf & U. Rüb

  10. Department of Pathology and Medical Biology, University Medical Center Groningen University of Groningen, NL-5970 RB, Groningen, The Netherlands

    W. F. den Dunnen

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  1. W. Scherzed
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  4. R. A. de Vos
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  8. G. Auburger
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  9. D. Del Turco
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Correspondence to U. Rüb.

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WF den Dunnen and U Rüb are joint senior authors.

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Scherzed, W., Brunt, E.R., Heinsen, H. et al. Pathoanatomy of Cerebellar Degeneration in Spinocerebellar Ataxia Type 2 (SCA2) and Type 3 (SCA3). Cerebellum 11, 749–760 (2012). https://doi.org/10.1007/s12311-011-0340-8

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