Journal
JOURNAL OF NEUROTRAUMA
Volume 38, Issue 6, Pages 803-817Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2020.7284
Keywords
bladder; external urethral sphincter; sex difference; spontaneous recovery
Funding
- NIH NINDS [R01NS099076, R01DA03190]
- NINDS [R01NS085426, R01NS106908, DoD/CDMRPW81XWH-14-1-0605]
- Shandong Provincial Key Research and Development Project [2019GSF107062]
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The study found that the spinal DA-ergic system regulates recovered micturition reflex in SCI male rats, with DR1 playing a key role in suppressing EUS activity and DR2 facilitating voiding.
Traumatic spinal cord injury (SCI) often causes micturition dysfunction. We recently discovered a low level of spinally-derived dopamine (DA) that regulates recovered bladder and sphincter reflexes in SCI female rats. Considering substantial sexual dimorphic features in the lower urinary tract, it is unknown if the DA-ergic mechanisms act in the male. Histological analysis showed a similar distribution of tyrosine hydroxylase (TH)(+) neurons in the lower cord of male rats and the number increased following thoracic SCI. Subsequently, focal electrical stimulation in slices obtained from L6/S1 spinal segments of SCI rats elicited detectable DA release with fast scan cyclic voltammetry. Using bladder cystometrogram and external urethral sphincter (EUS) electromyography in SCI male rats, intravenous (i.v.) administration of SCH 23390, a D-1-like receptor (DR1) antagonist, induced significantly increased tonic EUS activity and a trend of increased residual volume, whereas activation of these receptors with SKF 38393 did not influence the reflex. Meanwhile, blocking spinal D-2-like receptors (DR2) with remoxipride had no effect but stimulating these receptors with quinpirole elicited EUS bursting to increase voiding volume. Further, intrathecal delivery of SCH 23390 and quinpirole resulted in similar responses to those with i.v. delivery, respectively, which indicates the central action regardless of delivery route. In addition, metabolic cage assays showed that quinpirole increased the voiding frequency and total voiding volume in spontaneous micturition. Collectively, spinal DA-ergic machinery regulates recovered micturition reflex following SCI in male rats; spinal DR1 tonically suppress tonic EUS activity to enable voiding and activation of DR2 facilitates voiding.
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