Upregulated 5-HT Receptors Regulate Lower Urinary Tract Function in Rats After Complete Spinal Cord Injury

Overview

Journal J Neurotrauma

Publisher Mary Ann Liebert

Specialties Emergency Medicine
Neurology

Date 2023 Feb 10

PMID 36762948

Authors

Ching-Yi Lin

Kevin Li

Rajaa Thalluri

Yu-Shang Lee

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury (SCI) above the lumbosacral level often leads to dysfunction of the lower urinary tract (LUT) including detrusor hyper-reflexia, wherein bladder compliance is low, baseline pressures are increased, and filling is accompanied by numerous non-voiding contractions (NVCs) referred to as neurogenic detrusor overactivity. Here, we investigate the expression levels of the serotonin 1A (5-HT) receptor in segments both rostral and caudal to the injured site, as well as the effects on micturition of blocking 5-HT receptor using pharmacological interventions in spinally intact rats or T8 complete SCI rats. The activities of detrusor and external urethral sphincter (EUS) were assessed with the rats in a conscious condition. Adult female rats were divided into two groups: (1) sham control (T8 laminectomy only) and (2) T8 complete spinal cord transection. The observation period was 2 months after the original SCI. In Western blot analyses, we identified significant upregulation of the 5-HT receptor in the T10-L2 and L6/S1 segments after chronic complete SCI. In pharmacological studies, a dose-response study of the 5-HT receptor antagonist, WAY100635, indicated alterations in detrusor and EUS activities in spinally intact rats. Interestingly, blocking the 5-HT receptor alone resulted in inhibitory effects on NVCs with a reduced number and decreased amplitude, but in an increased interval between NVCs in SCI rats. In addition, the duration of EUS bursting was also significantly increased by WAY100635. These inhibitory effects of WAY100635 on NVCs were diminished by subsequent application of a beta-adrenergic blocker (propranolol). The reduction of NVCs observed by WAY100635 may be the result of blocking the constitutive activities of the 5-HT receptor but activating the beta-adrenergic sympathetic pathway, which in turn relaxes bladder activity. Together, the neuroplasticity of the 5-HT receptor can be a potential therapeutic target for treatment of bladder dysfunction after SCI.

Citing Articles

Long-Term 5-HT Receptor Agonist NLX-112 Treatment Improves Functional Recovery After Spinal Cord Injury.

Lin C, Li K, Gitchell T, Lee Y Int J Mol Sci. 2025; 26(1.

PMID: 39796094 PMC: 11719485. DOI: 10.3390/ijms26010239.

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