Maintenance of bladder innervation in diabetes: a stereological study of streptozotocin-treated female rats

Abstract

Neuropathy and cystopathy are two common conditions in patients with chronic diabetes. Despite obvious bladder sensory and motor nerve dysfunction in diabetes, no studies have selectively explored whether sensory or motor innervation is affected in the bladder. In the present study, we tested the hypothesis that loss of bladder sensory and motor fibers is responsible for bladder sensory and motor dysfunction. Parasympathetic and sensory innervation of the bladder dome and neck were examined using immunohistochemistry (IHC) and stereology in adult female rats 12weeks after induction of diabetes by streptozotocin. Naïve and age matched rats were evaluated as controls. Diabetic rats had mean blood glucose level of >400mg/dl, and bladder weights and thicknesses that were more than doubled compared to naïve rats. In naïve rats, parasympathetic vesicular acetylcholine transporter (VAT) and sensory calcitonin gene-related peptide (CGRP) immunopositive nerve fibers were located in bladder smooth muscle and were more densely distributed in the neck compared to the dome. Within the urothelial region, CGRP nerve fibers were densely distributed while VAT nerve fibers were sparsely distributed in the bladder neck and both were virtually absent in the bladder dome. Streptozotocin induced diabetes did not change the total nerve fiber length of either VAT or CGRP stained fibers in either the neck or dome. These studies indicate that hyperglycemia, induced by streptozotocin treatment, does not result in a loss of parasympathetic VAT or CGRP sensory nerve fibers, per se, but the doubling of bladder weight and mass does indicate a decrease in innervation density.

Keywords: CGRP; Detrusor; Endothelium; Immunofluorescence; Stereology; VAT.