Therapeutic effects of inhibition of brain-derived neurotrophic factor on voiding dysfunction in mice with spinal cord injury
Abstract
We investigated the involvement of brain-derived neurotrophic factor (BDNF) in bladder and urethral dysfunction using spinal cord-injured mice. We evaluated bladder and urethral function of female mice with 4-wk spinal cord injury (SCI) by filling cystometry and electromyography (EMG) of the external urethral sphincter (EUS) under a conscious condition. Anti-BDNF antibodies (10 μg·kg−1·h−1) were administered in some mice for 1 wk before the evaluation. Bladder and spinal (L6−S1) BDNF protein levels were examined by ELISA. Transcript levels of transient receptor potential channels or acid-sensing ion channels (Asic) in L6−S1 dorsal root ganglia were evaluated by RT-PCR. Voided volume and voiding efficiency were significantly increased without any changes in nonvoiding contractions, and the duration of reduced EMG activity during the voiding phase was significantly prolonged in anti-BDNF antibody-treated SCI mice. Compared with spinal cord-intact mice, SCI mice showed increased concentrations of bladder and spinal BDNF. Anti-BDNF antibody treatment decreased bladder and spinal BDNF protein concentrations of SCI mice. Asic2 and Asic3 transcripts were significantly increased after SCI but decreased after anti-BDNF antibody administration. These results indicate that upregulated expression of bladder and spinal BDNF is involved in the emergence of inefficient voiding in SCI mice. Thus, BDNF-targeting treatment could be an effective modality for the treatment of voiding problems, including inefficient voiding and detrusor sphincter dyssynergia after SCI.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 01, 2019
- Source ID
- 10.1152/ajprenal.00239.2019
Entities
People
- Hidehiro Kakizaki
- Masahiro Kurobe
- Naoki Wada
- Naoki Yoshimura
- Nobutaka Shimizu
- Pradeep Tyagi
- Takahiro Shimizu
- William C. De Groat
Organizations
- Asahikawa Medical University
- United States Department of Defense
- University of Pittsburgh