Functional, structural, and neuronal alterations in urinary bladder during diabetes: investigations of a mouse model.
Urinary bladder dysfunction is a common complication in diabetes, but the mechanisms involved are undefined and treatment options are limited. Murine models provide opportunities to utilize transgenic technologies for bladder research and here we investigate the functional, structural and neuronal aspects of the bladder in a mouse model of type-1 diabetes. Mice were injected with streptozotocin (150 mg/kg) or vehicle and studied at 5 weeks. Increases in blood glucose and total urine output were observed. In vitro cystometry showed a 2-fold increase in bladder capacity and compliance and decreased intravesical plateau pressure in diabetics versus controls. Bladder structure and composition were evaluated by digital imaging; region-specific changes included increased smooth muscle and urothelium and no change in collagen content. Alterations in cholinergic, adrenergic and nitric oxide-related functional responsiveness were also observed. The prevalence of cholinergic and adrenergic neuronal tracts was determined by immunohistochemistry: decreased vesicular acetylcholine transferase was observed in smooth muscle, whereas tyrosine hydroxylase was increased in the lamina propria, demonstrating a 'neuronal remodeling' shift toward pro-relaxant neuronal pathways. These studies demonstrate that this mouse model of diabetes exhibits important features of urinary bladder remodeling that are similar to the findings in humans and other animal models and will therefore be useful for further mechanistic investigations.
Poladia
Deepali Pitre
DP
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus, Ohio, USA.
Bauer
John Anthony
JA
D000344:Afferent Pathways / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D003187:Compliance; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009130:Muscle, Smooth / Q000294:innervation / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D001743:Urinary Bladder / Q000294:innervation / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D014563:Urodynamics / Q000502:physiology*; D050494:Vesicular Acetylcholine Transport Proteins
D015415:Biomarkers; D001786:Blood Glucose; D026901:Membrane Transport Proteins; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D014446:Tyrosine 3-Monooxygenase