Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Department of Renal and Urologic Surgery, Asahikawa Medical University, Asahikawa, Japan.
Am J Physiol Renal Physiol. 2019 Nov 1;317(5):F1305-F1310. doi: 10.1152/ajprenal.00239.2019. Epub 2019 Sep 30.
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·h) 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.
我们使用脊髓损伤小鼠研究脑源性神经营养因子（BDNF）在膀胱和尿道功能障碍中的作用。我们通过在清醒状态下进行膀胱充盈测压和尿道外括约肌（EUS）肌电图（EMG）评估 4 周脊髓损伤（SCI）雌性小鼠的膀胱和尿道功能。在评估前 1 周，一些小鼠给予抗 BDNF 抗体（10 μg·kg·h）。通过 ELISA 检测膀胱和脊髓（L6-S1）BDNF 蛋白水平。通过 RT-PCR 评估 L6-S1 背根神经节中瞬时受体电位通道或酸敏感离子通道（Asic）的转录水平。在抗 BDNF 抗体治疗的 SCI 小鼠中，排空量和排空效率显著增加，而无排尿收缩时的 EMG 活动持续时间显著延长。与脊髓完整小鼠相比，SCI 小鼠的膀胱和脊髓 BDNF 浓度增加。抗 BDNF 抗体治疗降低了 SCI 小鼠的膀胱和脊髓 BDNF 蛋白浓度。SCI 后 Asic2 和 Asic3 转录本显著增加，但抗 BDNF 抗体给药后减少。这些结果表明，膀胱和脊髓 BDNF 的上调表达参与了 SCI 小鼠低效排尿的出现。因此，BDNF 靶向治疗可能是治疗 SCI 后排尿问题（包括低效排尿和逼尿肌括约肌协同失调）的有效方法。
