Abstract
BackgroundPatients with neurodegenerative diseases such as multiple sclerosis, Parkinson’s, and Alzheimer’s often present with lower urinary tract symptoms (LUTS, urinary frequency, urgency, nocturia and retention) resulting from damage to the peripheral and central nervous systems. These studies were designed to examine the changes in the function of the bladder that may underlie neurogenic bladder dysfunction using a mouse model of demyelination in the CNS.MethodsBladders from 12 week old male C57BL/6J mice with coronavirus-induced encephalomyelitis (CIE, a chronic, progressive demyelinating disease model of human MS), and age-matched controls, were cut into 5–7 strips and suspended in physiological muscle baths for tension measurement in response to agonists and electric field stimulation (EFS). Experiments were performed on intact and denuded (with mucosa removed) bladder strips.ResultsThe maximum effect of EFS was not significantly different between CIE and control bladders. Nerve-evoked EFS contractions (tetrodotoxin-sensitive) were blocked by a combination of atropine (cholinergic antagonist) and α,β-methylene ATP (an ATP analog that desensitizes purinergic receptors). In response to EFS, the α,β-methylene ATP-resistant (cholinergic) component of contraction was significantly reduced, while the atropine-resistant (purinergic) component was significantly increased in CIE bladders. Removal of the mucosa in CIE bladders restored the cholinergic component. Bethanechol (muscarinic receptor agonist) potency was significantly increased in CIE bladders.ConclusionsOur data demonstrate a deficit in the nerve-evoked cholinergic component of contraction that is not due to the ability of the smooth muscle to respond to acetylcholine. We conclude that neurodegenerative bladder dysfunction in this model of multiple sclerosis may be due, in part, to pathologic changes in the mucosa that causes suppression of muscarinic receptor-mediated contractile response and augmentation of purinergic response of the underlying muscle. Further studies utilizing CIE mice should help elucidate the pathological changes in the mucosa resulting from demyelination in the CNS.
Highlights
Multiple sclerosis (MS) is a chronic autoimmune disorder, in which the improper activation of the host’s immune system results in demyelinated lesions, predominantly in the brain and spinal cord
There was no difference in the CXA between mucosa denuded coronavirus-induced encephalomyelitis (CIE) (0.2160.01 mm2) and mucosa denuded control bladder strips (0.2160.01 mm2)
The thickness of the detrusor smooth muscle layer was similar in CIE and controls (153.3611 and 192.6633 mm, respectively)
Summary
Multiple sclerosis (MS) is a chronic autoimmune disorder, in which the improper activation of the host’s immune system results in demyelinated lesions, predominantly in the brain and spinal cord. Neuronal control over bladder function is coordinated by the pontine storage and micturition centers in the brain stem, which sends projections to regions of the lumbosacral spinal cord coordinating parasympathetic outflow to the detrusor. Patients with neurodegenerative diseases such as multiple sclerosis, Parkinson’s, and Alzheimer’s often present with lower urinary tract symptoms (LUTS, urinary frequency, urgency, nocturia and retention) resulting from damage to the peripheral and central nervous systems.
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