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BDNF-ERK1/2 signaling pathway in ketamine-associated lower urinary tract symptoms

Abstract

Objectives

Long-term ketamine abuse can affect the urinary system, resulting in lower urinary tract symptoms (LUTS), but the pathogenesis of this is still unknown. Previous studies have demonstrated that ketamine can change the expression of the brain-derived neurotrophic factor (BDNF) in the serum of ketamine abuse patients. The aim of the present study is to explore the mechanism of the ketamine-mediated BDNF signaling pathway in the bladder of rats on chronic ketamine treatment.

Methods

Rats were randomly assigned to a control (normal saline) or ketamine (30 mg/kg) group, with five rats in each group. The experimental group was given ketamine via intraperitoneal injection daily, while the control group was treated with saline. After 12 weeks of treatment, bladders were excised and samples from the control and ketamine group were examined with transmission electron microscopy (TEM). Phosphoprotein and non-phosphoprotein purification, histopathology, immunohistochemistry, and western blot were carried out in all groups.

Results

Histological study showed hyperplastic epithelium and inflammatory cell infiltration in ketamine-treated rat bladders. TEM showed that chronic ketamine treatment results in structural damage to organelles. Immunohistochemical staining and western blot showed that the expression of BDNF was significantly lower in the ketamine group. However, the expression of phosphorylated extracellular signal-regulated kinases ½ (ERK1/2) in the ketamine group was higher, whereas the total ERK1/2 was similar to the control group.

Conclusions

Long-term ketamine abuse reduces expression of BDNF, while inducing phosphorylation of ERK1/2 in the bladder wall. This may play an important role in the pathogenesis of ketamine-associated LUTS.

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Acknowledgments

Thanks are due to Tongzu Liu for assistance with the experiments and to Biwen Peng for valuable discussion.

Funding

This study was funded by Zhongnan Hospital of Wuhan University.

Author information

Correspondence to Tongzu Liu.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Wang, X., Peng, B., Xu, C. et al. BDNF-ERK1/2 signaling pathway in ketamine-associated lower urinary tract symptoms. Int Urol Nephrol 48, 1387–1393 (2016). https://doi.org/10.1007/s11255-016-1315-y

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Keywords

  • Ketamine
  • Lower urinary tract symptoms
  • BDNF
  • Apoptosis