# Mechanisms of neurogenic bladder dysfunction in a viral murine model of multiple sclerosis

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $342,100

## Abstract

PROJECT SUMMARY
 Multiple sclerosis (MS) is an auto-inflammatory disease of the central nervous system (CNS) that affects
approximately 400,000 people in the United States and more than 2.1 million people worldwide. Lower urinary
tract symptoms (LUTS) are present in 70–90% of MS patients, and include urinary frequency, urgency,
incontinence, nocturia, incomplete bladder emptying, weak stream, and retention of urine. We recently
characterized a new mouse model of neurogenic bladder dysfunction induced by a coronavirus. The virus
triggers acute inflammation in the CNS (coronavirus-induced encephalomyelitis, CIE model) followed by
progressive demyelination in the brain and spinal cord. CIE mice develop a significant neurologic deficit
associated with voiding dysfunction that is comparable with neurogenic LUTS observed in MS patients. The
mechanisms underlying neurogenic LUTS in CIE mice include morphological changes in the neuronal centers
controlling micturition, activation of spinal glia, increased expression of pro-inflammatory cytokines during acute
phase of infection, and enhanced purinergic responses of bladder contractions. Our recent study performed a
long-term follow up of CIE mice and revealed 3 differential phenotypes of neurodegenerative symptom
development: 1-chronic progression of neurodegeneration with continuous presence of symptoms (C-PRO
group), 2 – presence of several remission-relapsing episodes (C-RELAP group), and 3 - recovery from initial
symptoms after acute phase of the disease (REC group). Urodynamic evaluation of voiding patterns in each
subgroup revealed that mice in C-RELAP group showed the most severe neurogenic bladder overactivity
associated with lower bladder capacity, reduced inter-micturition interval, and decreased pressure at micturition.
Therefore, the CIE model provides a unique opportunity for the comparison of neurogenic LUTS in three major
types of human MS (remissive, chronic and relapsing-remitting). This application builds upon our initial findings,
and will uncover the detailed systemic and cellular mechanisms of neurogenic LUTS in order to improve the
assessment, diagnosis, and care of LUTS in MS patients. Specific Aim 1 will determine the role of spinal glia
activation (gliosis) in modulation of neuronal signaling in the central (spinal) and peripheral (sensory and motor
autonomic ganglia) centers involved in the control of micturition. We will evaluate the mechanistic link between
glial activation in the spinal cord and functional changes in bladder innervating neurons during early, advanced
and chronic stages of MS progression. Specific Aim 2 will test the ability of targeted immunotherapy to improve
neurogenic LUTS in a murine model of MS. The proposed experiments will utilize neuroanatomical, biochemical,
electrophysiological, pharmacological, pharmacogenetic, immunotherapeutic, and behavioral experiments to
provide a comprehensive assessment of the mechanisms underlying the development of neurogen...

## Key facts

- **NIH application ID:** 10450102
- **Project number:** 5R01DK116648-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Anna P Malykhina
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $342,100
- **Award type:** 5
- **Project period:** 2020-09-08 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450102

## Citation

> US National Institutes of Health, RePORTER application 10450102, Mechanisms of neurogenic bladder dysfunction in a viral murine model of multiple sclerosis (5R01DK116648-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10450102. Licensed CC0.

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