Figure 8
From: Sexual dimorphic impacts of systemic vincristine on lower urinary tract function
Schematic diagram of the proposed mechanisms underlying vincristine induced alterations in lower urinary tract function. Systemic VCR exposure induces deficiency in bladder sensation, leading to a decrease in micturition frequency accompanied with an increased bladder capacity. In addition to the VCR-induced impairments of axonal transport and distal axonopathy, sexual dimorphic mechanisms contribute to the phenotype; in females, a decrease in bladder afferent firing through downregulation of Htr3b signaling while in males, neuroinflammation. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can exacerbate the symptoms. In males, the dysregulations of cellular ion homeostasis in the bladder through enhanced Trpa1 signaling induce increases in cell excitability, leading to detrusor overactivity. The VCR-induced neuroinflammation also can play a role in detrusor overactivity in male. Systemic VCR exposure can increase risk of developing long-term sex specific LUTD via multiple mechanisms.
