Get access

Bladder dysfunction in a transgenic mouse model of multiple system atrophy

Authors

  • Mathieu Boudes PhD,

    1. Laboratory of Biomarkers, Screening and Diagnosis, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
    2. Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
    Search for more papers by this author
  • Pieter Uvin MD,

    1. Laboratory of Biomarkers, Screening and Diagnosis, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
    2. Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
    Search for more papers by this author
  • Silvia Pinto,

    1. Laboratory of Biomarkers, Screening and Diagnosis, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
    Search for more papers by this author
  • Thomas Voets PhD,

    1. Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
    Search for more papers by this author
  • Clare J. Fowler MD,

    1. University College London, Department of Uro-Neurology, London, United Kingdom
    Search for more papers by this author
  • Gregor K. Wenning MD, PhD,

    1. Division of Neurobiology, Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
    Search for more papers by this author
  • Dirk De Ridder MD, PhD,

    1. Laboratory of Biomarkers, Screening and Diagnosis, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
    Search for more papers by this author
  • Nadia Stefanova MD, PhD

    Corresponding author
    • Division of Neurobiology, Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
    Search for more papers by this author

  • Funding agencies: This research work was supported by Research Foundation Flanders (FWO) grants G.0172.03, G.149.03, G0565.07, and G0686.09, Research Council of the KU Leuven grants GOA2004/07 and EF/95/010, an unrestricted educational grant by Astellas (to Dirk De Ridder) and a grant of the Austrian Science Funds (FWF) F4404-B19 (to Gregor K. Wenning and Nadia Stefanova). Mathieu Boudes is a Marie Curie Fellow, and Pieter Uvin is a PhD student of the FWO. Dirk De Ridder is a clinician-fundamental researcher of the FWO Vlaanderen.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

Correspondence to: Dr. Nadia Stefanova, Division of Neurobiology, Department of Neurology, Anichstr. 35, 6020 Innsbruck, Austria; nadia.stefanova@i-med.ac.at

ABSTRACT

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder presenting with motor impairment and autonomic dysfunction. Urological function is altered in the majority of MSA patients, and urological symptoms often precede the motor syndrome. To date, bladder function and structure have never been investigated in MSA models. We aimed to test bladder function in a transgenic MSA mouse featuring oligodendroglial α-synucleinopathy and define its applicability as a preclinical model to study urological failure in MSA. Experiments were performed in proteolipid protein (PLP)–human α-synuclein (hαSyn) transgenic and control wild-type mice. Diuresis, urodynamics, and detrusor strip contractility were assessed to characterize the urological phenotype. Bladder morphology and neuropathology of the lumbosacral intermediolateral column and the pontine micturition center (PMC) were analyzed in young and aged mice. Urodynamic analysis revealed a less efficient and unstable bladder in MSA mice with increased voiding contraction amplitude, higher frequency of nonvoiding contractions, and increased postvoid residual volume. MSA mice bladder walls showed early detrusor hypertrophy and age-related urothelium hypertrophy. Transgenic hαSyn expression was detected in Schwann cells ensheathing the local nerve fibers in the lamina propria and muscularis of MSA bladders. Early loss of parasympathetic outflow neurons and delayed degeneration of the PMC accompanied the urological deficits in MSA mice. PLP-hαSyn mice recapitulate major urological symptoms of human MSA that may be linked to αSyn-related central and peripheral neuropathology and can be further used as a preclinical model to decipher pathomechanisms of MSA. © 2013 Movement Disorder Society

Get access to the full text of this article

Ancillary