title: Autonomic dysfunction and plasticity in micturition reflexes in human α-synuclein mice.
abstract: Although often overshadowed by the motor dysfunction associated with Parkinson's disease (PD), autonomic dysfunction including urinary bladder and bowel dysfunctions are often associated with PD and may precede motoric changes; such autonomic dysfunction may permit early detection and intervention. Lower urinary tract symptoms are common in PD patients and result in significant morbidity. This studies focus on nonmotor symptoms in PD using a transgenic mouse model with overexpression of human α-synuclein (hSNCA), the peptide found in high concentrations in Lewy body neuronal inclusions, the histopathologic hallmark of PD. We examined changes in the physiological, molecular, chemical, and electrical properties of neuronal pathways controlling urinary bladder function in transgenic mice. The results of these studies reveal that autonomic dysfunction (i.e., urinary bladder) can precede motor dysfunction. In addition, mice with hSNCA overexpression in relevant neuronal populations is associated with alterations in expression of neurotransmitter/neuromodulatory molecules (PACAP, VIP, substance P, and neuronal NOS) within neuronal pathways regulating bladder function as well as with increased NGF expression in the urinary bladder. Changes in the electrical and synaptic properties of neurons in the major pelvic ganglia that provide postganglionic innervation to urogenital tissues were not changed as determined with intracellular recording. The urinary bladder dysfunction observed in transgenic mice likely reflects changes in peripheral (i.e., afferent) and/or central micturition pathways or changes in the urinary bladder. SYN-OE mice provide an opportunity to examine early events underlying the molecular and cellular plasticity of autonomic nervous system pathways underlying synucleinopathies.
authors.affiliation: Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05405, USA. Robert.Hamill@uvm.edu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hamill
authors.forename: John D
authors.initials: JD
authors.lastname: Tompkins
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Girard
authors.forename: Richard T
authors.initials: RT
authors.lastname: Kershen
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Parsons
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Vizzard
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D001743:Urinary Bladder / Q000378:metabolism / Q000503:physiopathology; D014554:Urination / Q000502:physiology*; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein