title: BDNF-ERK1/2 signaling pathway in ketamine-associated lower urinary tract symptoms.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 169 Donghu Rd, Wuhan, 430071, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Wuhan University, 185 Donghu Rd, Wuhan, 430071, China.
authors.forename: Biwen
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 169 Donghu Rd, Wuhan, 430071, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 169 Donghu Rd, Wuhan, 430071, China.
authors.forename: Zhengyan
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 169 Donghu Rd, Wuhan, 430071, China.
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 169 Donghu Rd, Wuhan, 430071, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 169 Donghu Rd, Wuhan, 430071, China. wangxl890204@163.com.|Department of Physiology, School of Basic Medical Sciences, Wuhan University, 185 Donghu Rd, Wuhan, 430071, China. wangxl890204@163.com.
authors.forename: Tongzu
authors.initials: T
authors.lastname: Liu
mesh_terms: D000700:Analgesics / Q000009:adverse effects*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005260:Female; D007649:Ketamine / Q000009:adverse effects*; D059411:Lower Urinary Tract Symptoms / Q000139:chemically induced / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D046529:Microscopy, Electron, Transmission; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB; D001743:Urinary Bladder / Q000378:metabolism; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor; D007649:Ketamine; C579455:BDNF protein, human; C000621230:Ntrk2 protein, rat; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Apoptosis; BDNF; Ketamine; Lower urinary tract symptoms