Development of urinary impairment after spinal cord injury courses with altered urethral serotonin signalling in the female mice
Year: 2025
Type: article
Abstract: Spinal Cord Injury (SCI) often leads to urinary incontinence. While alterations in the bladder have been considered the primary cause of post-SCI urinary dysfunction, evidence suggests that urethral afferents may influence post-SCI bladder activity. These afferents respond to locally produced serotonin (5-HT), and 5-HT signalling may likely be affected by SCI. Here, we investigated the role of urethral 5-HT on post-SCI bladder reflex activity using female C57BL/6 mice (wild-type -WT- and animals lacking urethral 5-HT (tryptophan hydroxylase 1 -tph1- null - tph1 −/− ). In WT animals, bladder overactivity and increased 5-HT + urethral cells were observed at one and four weeks post-SCI (1w and 4w, respectively), while, in contrast, tph1 −/− mice showed some preservation of bladder function. Both genotypes developed urethral smooth muscle atrophy 4w post-SCI, but fibrosis of striated muscle was detected only in tph1 −/− 4w SCI mice. Sensory and cholinergic fibres were upregulated only in WT SCI mice, suggesting 5-HT depletion may block their expansion. Pharmacological blockade of 5-HT receptors did not prevented urinary impairment but affected SCI-induced bladder dysfunction. These observations indicate that urethral 5-HT contributes to SCI-induced urinary impairment and urethral tissue reorganization, offering new insights into the urethrovesical reflex and potentially pinpointing new therapeutic targets.
Source: Scientific Reports
Authors: Ana Ferreira, Sílvia Sousa Chambel, Carlos Reguenga, António Avelino, Célia Duarte Cruz
Language: English
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W4417115369