title: Expression of brain derived-neurotrophic factor and granulocyte-colony stimulating factor in the urothelium: relation with voiding function.
abstract: BACKGROUND
  We designed this experiment to elucidate the relationship between the expression of brain derived-neurotrophic factor (BDNF), the expression of granulocyte-colony stimulating factor (G-CSF), and the development of overactive bladder (OAB). In our previous study, the urothelium was observed to be more than a simple mechanosensory receptor and was found to be a potential therapeutic target for OAB. Moreover, neuregulin-1 and BDNF were found to be potential new biomarkers of OAB. Here, we investigated the relationship between changes in the voiding pattern and the expression of BDNF and G-CSF in the urothelium and evaluated the effects of 5-hydroxymethyl tolterodine (5-HMT) on rats with bladder outlet obstruction (BOO).
  
  
  METHODS
  A total of 100 Sprague-Dawley rats were divided into the following groups: 20 control rats; 40 BOO rats; and 40 BOO rats administered 5-HMT (0.1 mg/kg). After BOO was induced for 4 weeks, the rats were assessed by cystometrography. The changes in BDNF and G-CSF expression were examined in both separated urothelial tissues and in cultured urothelial cells by reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  BOO rats showed increased non-voiding activity [NVA; (number/10 voidings)] and bladder weight and decreased micturition volume (MV), micturition interval (MI), and micturition time (MT) relative to the controls. Moreover, the 5-HMT administration rats showed decreased NVA and bladder weight and increased MV and MI in comparison to the BOO rats. BDNF and G-CSF expression was increased in BOO rats and decreased following 5-HMT administration. In this model, voiding dysfunction developed as a result of BOO. As a therapeutic agent for OAB, the administration of 5-HMT improved the voiding dysfunction.
  
  
  CONCLUSIONS
  BDNF and G-CSF might modulate voiding patterns through micturition pathways and might be involved only in the urothelium. Moreover, the expression of both genes in the urothelium might be related to voiding dysfunction in OAB patients. Thus, the urothelium has an important role in the manifestation of voiding symptoms.
authors.affiliation: Department of Urology, Korea St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. assa7913@naver.com.
authors.forename: Seung Mo
authors.initials: SM
authors.lastname: Yuk
authors.affiliation: Department of Urology, Korea Chungnam National University Hospital, College of Medicine, Chungnam National University, Daejeon, South Korea. synthia2000@naver.com.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Urology, Korea Chungnam National University Hospital, College of Medicine, Chungnam National University, Daejeon, South Korea. urosong@cnu.ac.kr.
authors.forename: Ki Hak
authors.initials: KH
authors.lastname: Song
authors.affiliation: Department of Urology, Korea Chungnam National University Hospital, College of Medicine, Chungnam National University, Daejeon, South Korea. yongna@cnu.ac.kr.
authors.forename: Yong Gil
authors.initials: YG
authors.lastname: Na
authors.affiliation: Department of Urology, Korea Chungnam National University Hospital, College of Medicine, Chungnam National University, Daejeon, South Korea. uro17@cnu.ac.kr.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Urology, Korea Chungnam National University Hospital, College of Medicine, Chungnam National University, Daejeon, South Korea. doctor6@daum.net.
authors.forename: Chong Koo
authors.initials: CK
authors.lastname: Sul
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D053201:Urinary Bladder, Overactive / Q000378:metabolism / Q000503:physiopathology*; D014554:Urination / Q000502:physiology*; D019459:Urothelium / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016179:Granulocyte Colony-Stimulating Factor