Ekman Mari, Zhu Baoyi, Swärd Karl, Uvelius Bengt
Department of Experimental Medical Science, Lund University, Lund, Sweden; Department of Biology, Lund University, Lund, Sweden.
Department of Experimental Medical Science, Lund University, Lund, Sweden; Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Guang Dong, China.
Auton Neurosci. 2017 Jul;205:41-49. doi: 10.1016/j.autneu.2017.03.004. Epub 2017 Mar 18.
Neurotrophic factors regulate survival and growth of neurons. The urinary bladder is innervated via both sympathetic and parasympathetic neurons located in the major pelvic ganglion. The aim of the present study was to characterize the effects of the neurotrophins nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) on the sprouting rate of sympathetic and parasympathetic neurites from the female mouse ganglion. The pelvic ganglion was dissected out and attached to a petri dish and cultured in vitro. All three factors (BDNF, NT-3 and NGF) stimulated neurite outgrowth of both sympathetic and parasympathetic neurites although BDNF and NT-3 had a higher stimulatory effect on parasympathetic ganglion cells. The neurotrophin receptors TrkA, TrkB and TrkC were all expressed in neurons of the ganglia. Co-culture of ganglia with urinary bladder tissue, but not diaphragm tissue, increased the sprouting rate of neurites. Active forms of BDNF and NT-3 were detected in urinary bladder tissue using western blotting whereas tissue from the diaphragm expressed NGF. Neurite outgrowth from the pelvic ganglion was inhibited by a TrkB receptor antagonist. We therefore suggest that the urinary bladder releases trophic factors, including BDNF and NT-3, which regulate neurite outgrowth via activation of neuronal Trk-receptors. These findings could influence future strategies for developing pharmaceuticals to improve re-innervation due to bladder pathologies.
神经营养因子调节神经元的存活和生长。膀胱由位于主盆腔神经节的交感神经和副交感神经支配。本研究的目的是表征神经营养因子神经生长因子（NGF）、脑源性神经营养因子（BDNF）和神经营养因子3（NT-3）对雌性小鼠神经节中交感和副交感神经突萌发率的影响。解剖出盆腔神经节并附着在培养皿上进行体外培养。所有三种因子（BDNF、NT-3和NGF）均刺激交感和副交感神经突的神经突生长，尽管BDNF和NT-3对副交感神经节细胞具有更高的刺激作用。神经营养因子受体TrkA、TrkB和TrkC均在神经节的神经元中表达。将神经节与膀胱组织而非膈肌组织共培养可提高神经突的萌发率。使用蛋白质印迹法在膀胱组织中检测到BDNF和NT-3的活性形式，而膈肌组织表达NGF。TrkB受体拮抗剂抑制了盆腔神经节的神经突生长。因此，我们认为膀胱释放包括BDNF和NT-3在内的营养因子，这些因子通过激活神经元Trk受体来调节神经突生长。这些发现可能会影响未来开发改善膀胱病变导致的再支配的药物的策略。
