PMID- 25653370 OWN - NLM STAT- MEDLINE DCOM- 20150414 LR - 20230322 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 35 IP - 5 DP - 2015 Feb 4 TI - The role of brain-derived neurotrophic factor (BDNF) in the development of neurogenic detrusor overactivity (NDO). PG - 2146-60 LID - 10.1523/JNEUROSCI.0373-14.2015 [doi] AB - Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients. CI - Copyright (c) 2015 Frias et al. FAU - Frias, Barbara AU - Frias B AD - Department of Experimental Biology, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal, Translational NeuroUrology and. FAU - Santos, Joao AU - Santos J AD - Department of Experimental Biology, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal. FAU - Morgado, Marlene AU - Morgado M AD - Nerve Regeneration Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal. FAU - Sousa, Monica Mendes AU - Sousa MM AD - Nerve Regeneration Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal. FAU - Gray, Susannah M Y AU - Gray SM AD - Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, BT7 1 NN Belfast, United Kingdom. FAU - McCloskey, Karen D AU - McCloskey KD AD - Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, BT7 1 NN Belfast, United Kingdom. FAU - Allen, Shelley AU - Allen S AD - Molecular Neurobiology Unit, University of Bristol, School of Clinical Sciences, BS10 5NB Bristol, United Kingdom. FAU - Cruz, Francisco AU - Cruz F AD - Translational NeuroUrology and Department of Urology, Hospital de S. Joao, 4200-319 Porto, Portugal, and. FAU - Cruz, Celia Duarte AU - Cruz CD AD - Department of Experimental Biology, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal, Translational NeuroUrology and ccruz@med.up.pt. LA - eng GR - 106/ALZS_/Alzheimer's Society/United Kingdom GR - MR/M012425/1/MRC_/Medical Research Council/United Kingdom GR - BB/G530176/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Axons/metabolism/physiology MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cells, Cultured MH - Female MH - Nerve Regeneration MH - Rats MH - Rats, Wistar MH - Spinal Cord Dorsal Horn/metabolism/physiopathology MH - Spinal Cord Injuries/complications/*metabolism/physiopathology MH - Urinary Bladder, Neurogenic/etiology/*metabolism/physiopathology PMC - PMC4315839 OTO - NOTNLM OT - BDNF OT - incontinence OT - neurotrophins OT - spinal cord OT - urinary bladder COIS- The authors declare no competing financial interests. EDAT- 2015/02/06 06:00 MHDA- 2015/04/15 06:00 PMCR- 2015/02/04 CRDT- 2015/02/06 06:00 PHST- 2015/02/06 06:00 [entrez] PHST- 2015/02/06 06:00 [pubmed] PHST- 2015/04/15 06:00 [medline] PHST- 2015/02/04 00:00 [pmc-release] AID - 35/5/2146 [pii] AID - 0373-14 [pii] AID - 10.1523/JNEUROSCI.0373-14.2015 [doi] PST - ppublish SO - J Neurosci. 2015 Feb 4;35(5):2146-60. doi: 10.1523/JNEUROSCI.0373-14.2015.