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Project

The intraspinal serotonergic system regulates micturition reflexe after SCI

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Lower urinary tract dysfunctions are significant clinical issues in patients with spinal cord injury (SCI) and an effective treatment to improve the quality of life for these patients is not available. The regulation of normal/volunteer micturition reflexes requires a complicated network between brain, spinal cord, and lower urinary tract organs including detrusor and external urethral sphincter (EUS). SCI leads to disconnection of supraspinal inputs and lower urinary function becomes a local reflex mode with further developing neurogenic bladder, including detrusor overactivity and detrusor sphincter dyssynergia. The spinal cord segments below the injured site start to remodel and to show plasticity in order to respond to the injury. Further understanding of the neuroplasticity below the injured site and its involvement in micturition control will provide more insights for developing strategies to treat neurogenic bladder after SCI. Descending serotonergic (5-HT) projections has been shown to be important in regulating normal bladder reflexes involving both detrusor and EUS activity. However, the role and plasticity of the intrinsic spinal serotonergic system and serotonergic receptors in the regulation of micturition reflexes after SCI still remain to be determined. In addition, there are species-dependent differences in the influence of 5HT-1A receptors on micturition according to previous pharmacological studies. Here, we will test the overall hypothesis that intrinsic spinal 5-HT-immunoreactive like (5HT-IL) neurons, serotonergic fibers, and the plasticity of serotonergic receptors below the injured site are involved in the bladder reflex network together with the regulation of voiding in adult rat model. In Specific Aim 1, we will use immunohistological staining to collect anatomical data regarding the distribution of 5HT-IL neurons and serotonergic fibers within the micturition reflex pathways. Pharmacological interventions to degenerate these intrinsic spinal serotonergic resources will be used to test their roles in regulating voiding behaviors (both detrusor and EUS activity). In Specific Aim 2, we will further test the hypothesis that the plasticity of 5-HT receptors contributes to the pathological neurogenic bladder after T8 complete SCI. We will characterize the expression patterns (different timing and intensity) of 5-HT receptors and their roles in contributing to bladder dysfunction after SCI. Pharmacologically selective activation or blockade of 5-HT receptors will be used to test the roles of serotonergic receptors in regulating voiding behavior (both detrusor and EUS activity) after SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • RCDC

    Urologic Diseases

  • HRCS HC

    Neurological

  • HRCS HC

    Renal and Urogenital

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science