The role of brain-derived neurotrophic factor (BDNF) in the development of neurogenic detrusor overactivity (NDO)

Bárbara Frias, João Santos, Marlene Morgado, Mónica Mendes Sousa, Susannah M Y Gray, Karen D McCloskey, Shelley Allen, Francisco Cruz, Célia Duarte Cruz

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27 Citations (Scopus)
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Abstract

Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients.

Original languageEnglish
Pages (from-to)2146-60
Number of pages15
JournalJournal of Neuroscience
Volume35
Issue number5
DOIs
Publication statusPublished - 4 Feb 2015

Bibliographical note

Copyright © 2015 Frias et al.

Keywords

  • Animals
  • Axons
  • Brain-Derived Neurotrophic Factor
  • Cells, Cultured
  • Female
  • Nerve Regeneration
  • Rats
  • Rats, Wistar
  • Spinal Cord Dorsal Horn
  • Spinal Cord Injuries
  • Urinary Bladder, Neurogenic

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  • Cite this

    Frias, B., Santos, J., Morgado, M., Sousa, M. M., Gray, S. M. Y., McCloskey, K. D., Allen, S., Cruz, F., & Cruz, C. D. (2015). The role of brain-derived neurotrophic factor (BDNF) in the development of neurogenic detrusor overactivity (NDO). Journal of Neuroscience, 35(5), 2146-60. https://doi.org/10.1523/JNEUROSCI.0373-14.2015