Differential neurodegenerative phenotypes are associated with heterogeneous voiding dysfunction in a coronavirus-induced model of multiple sclerosis.

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ID: 86355
2019
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Abstract
Patients with multiple sclerosis (MS) develop a variety of lower urinary tract symptoms (LUTS). We previously characterized a murine model of neurogenic bladder dysfunction induced by a neurotropic strain of a coronavirus. In the present study, we further study the role of long-lasting neurodegeneration on the development of neurogenic bladder dysfunction in mice with corona-virus induced encephalitis (CIE). Long-term follow up study revealed three phenotypes of neurodegenerative symptom development: recovery (REC group), chronic progression (C-PRO group) and chronic disease with relapsing-remitting episodes (C-RELAP group). The levels of IL-1β in REC group, IL-10 in C-RELAP group, and IL-1β, IL-6, IL-10 and TNF-α in C-PRO group were diminished in the brain. The levels of TNF-α in REC group and INF-γ, IL-2, TGF-β and TNF-α in the C-PRO group were also diminished in the urinary bladder. Mice in C-RELAP group showed a delayed recovery of voiding function. In vitro contractility studies determined a decreased basal detrusor tone and reduced amplitude of nerve-mediated contractions in C-RELAP group, whereas C-PRO group had elevated muscle-mediated contractions. In conclusion, mice with CIE developed three phenotypes of neurologic impairment mimicking different types of MS progression in humans and showed differential mechanisms driving neurogenic bladder dysfunction.
Reference Key
lee2019differentialscientific Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Lee, Sanghee;Nedumaran, Balachandar;Hypolite, Joseph;Caldwell, Brian;Rudolph, Michael C;Malykhina, Anna P;
Journal Scientific reports
Year 2019
DOI
10.1038/s41598-019-47407-x
URL
Keywords
hiv-1 coumarin derivatives rnase h dual inhibitors integrase ledgf/p75 cellular cofactor

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