Bladder dysfunction in a transgenic mouse model of multiple system atrophy

<jats:title>ABSTRACT</jats:title><jats:p>Multiple system atrophy (<jats:styled-content style="fixed-case">MSA</jats:styled-content>) is an adult‐onset neurodegenerative disorder presenting with motor impairment and autonomic dysfunction. Urological function is altered in the majority of <jats:styled-content style="fixed-case">MSA</jats:styled-content> 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 <jats:styled-content style="fixed-case">MSA</jats:styled-content> mouse featuring oligodendroglial α‐synucleinopathy and define its applicability as a preclinical model to study urological failure in <jats:styled-content style="fixed-case">MSA</jats:styled-content>. Experiments were performed in proteolipid protein (<jats:styled-content style="fixed-case">PLP</jats:styled-content>)–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 (<jats:styled-content style="fixed-case">PMC</jats:styled-content>) were analyzed in young and aged mice. Urodynamic analysis revealed a less efficient and unstable bladder in <jats:styled-content style="fixed-case">MSA</jats:styled-content> 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 <jats:styled-content style="fixed-case">MSA</jats:styled-content> bladders. Early loss of parasympathetic outflow neurons and delayed degeneration of the <jats:styled-content style="fixed-case">PMC</jats:styled-content> accompanied the urological deficits in <jats:styled-content style="fixed-case">MSA</jats:styled-content> mice. <jats:styled-content style="fixed-case">PLP</jats:styled-content>‐hαSyn mice recapitulate major urological symptoms of human <jats:styled-content style="fixed-case">MSA</jats:styled-content> that may be linked to αSyn‐related central and peripheral neuropathology and can be further used as a preclinical model to decipher pathomechanisms of <jats:styled-content style="fixed-case">MSA</jats:styled-content>. © 2013 <jats:italic>Movement</jats:italic> Disorder Society</jats:p>