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Brain-derived neurotrophic factor in urinary continence and incontinence

Nature Reviews Urology volume 11, pages 579–588 (2014)Cite this article

Subjects

Key Points

  • Interactions between brain-derived neurotrophic factor (BDNF) and glutamate receptors participate in regulation of lower urinary tract function

  • BDNF-mediated glutamate signalling could have a role in the pharmacological mechanism of action of duloxetine

  • BDNF helps to maintain the continence mechanism by facilitation of pudendal nerve restoration after injury during childbirth

  • Both pudendal neuromodulation and onabotulinumtoxinA injection demonstrate a possible BDNF-related mechanism of action

  • Manipulation of BDNF levels, by electrical stimulation or other indirect methods, is a potential therapeutic strategy in the management of lower urinary tract symptoms

Abstract

Urinary incontinence adversely affects quality of life and results in an increased financial burden for the elderly. Accumulating evidence suggests a connection between neurotrophins, such as brain-derived neurotrophic factor (BDNF), and lower urinary tract function, particularly with regard to normal physiological function and the pathophysiological mechanisms of stress urinary incontinence (SUI) and bladder pain syndrome/interstitial cystitis (BPS/IC). The interaction between BDNF and glutamate receptors affects both bladder and external urethral sphincter function during micturition. Clinical findings indicate reduced BDNF levels in antepartum and postpartum women, potentially correlating with postpartum SUI. Experiments with animal models demonstrate that BDNF is decreased after simulated childbirth injury, thereby impeding the recovery of injured nerves and the restoration of continence. Treatment with exogenous BDNF facilitates neural recovery and the restoration of continence. Serotonin and noradrenaline reuptake inhibitors, used to treat both depression and SUI, result in enhanced BDNF levels. Understanding the neurophysiological roles of BDNF in maintaining normal urinary function and in the pathogenesis of SUI and BPS/IC could lead to future therapies based on these mechanisms.

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Figure 1: The neuromodulatory effects of BDNF in the dorsal root ganglion, in relation to lower urinary tract function.
Figure 2: Schematic diagram of the interaction between BDNF and glutamate receptors.
Figure 3: BDNF regulation of lower urinary tract function.

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Acknowledgements

This work was supported in part by the Rehabilitation Research & Development Service of the US Department of Veterans Affairs Office of Research and Development and The Cleveland Clinic.

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Authors and Affiliations

  1. Department of Urology, Changhai Hospital, Shanghai, PR China

    Qi-Xiang Song

  2. Department of Urology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, 15261, PA, USA

    Christopher J. Chermansky

  3. Department of Medicine, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, 15261, PA, USA

    Lori A. Birder

  4. Department of Urology, Second Affiliated Hospital of TMMU, Chongqing, PR China

    Longkun Li

  5. Department of Biomedical Engineering, The Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, 44195, OH, USA

    Margot S. Damaser

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Contributions

Q.-X.S. and M.S.D. researched the data for the article. Q.-X.S., C.J.C. and M.S.D. contributed substantially to discussion of the content. Q.-X.S., C.J.C., L.L. and M.S.D. wrote the article. All authors contributed to reviewing and editing the article before submission.

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Correspondence to Margot S. Damaser.

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Song, QX., Chermansky, C., Birder, L. et al. Brain-derived neurotrophic factor in urinary continence and incontinence. Nat Rev Urol 11, 579–588 (2014). https://doi.org/10.1038/nrurol.2014.244

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