title: Alterations in nerve-evoked bladder contractions in a coronavirus-induced mouse model of multiple sclerosis.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  Bladders 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Neil S
authors.initials: NS
authors.lastname: Lamarre
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Braverman
authors.affiliation: Division of Urology, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Glenolden, Pennsylvania, United States of America.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Malykhina
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Barbe
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ruggieri
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D017934:Coronavirus; D004195:Disease Models, Animal; D051379:Mice; D009103:Multiple Sclerosis / Q000503:physiopathology* / Q000821:virology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D018723:Bethanechol; D001285:Atropine; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate