PMID- 26687970
OWN - NLM
STAT- MEDLINE
DCOM- 20170508
LR  - 20181113
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 285
IP  - Pt B
DP  - 2016 Nov
TI  - Colitis-induced bladder afferent neuronal activation is regulated by BDNF through 
      PLCgamma pathway.
PG  - 126-135
LID - S0014-4886(15)30133-3 [pii]
LID - 10.1016/j.expneurol.2015.12.006 [doi]
AB  - Patients with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) 
      often experience increased sensory responsiveness in the urinary bladder 
      reflecting neurogenic bladder overactivity. Here we demonstrate that 
      colitis-induced up-regulation of the phospholipase C gamma (PLCgamma) pathway 
      downstream of brain-derived neurotrophic factor (BDNF) in bladder afferent 
      neurons in the dorsal root ganglia (DRG) plays essential roles in activating 
      these neurons thereby leading to bladder hyperactivity. Upon induction of colitis 
      with 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats, we found that the 
      phosphorylation (activation) level of cAMP responsive element-binding (p-CREB) 
      protein, a molecular switch of neuronal plasticity, was increased in specifically 
      labeled bladder afferent neurons in the thoracolumbar and lumbosacral DRGs. In 
      rats having reduced levels of BDNF (BDNF(+/-)), colitis failed to elevate CREB 
      protein activity in bladder afferent neurons. Physiological examination also 
      demonstrated that colitis-induced urinary frequency was not shown in BDNF(+/-) 
      rats, implicating an essential role of BDNF in mediating colon-to-bladder sensory 
      cross-sensitization. We further implemented in vivo and in vitro studies and 
      demonstrated that BDNF-mediated colon-to-bladder sensory cross-activation 
      involved the TrkB-PLCgamma-calcium/calmodulin-dependent protein kinase II (CaMKII) 
      cascade. In contrast, the PI3K/Akt pathway was not activated in bladder afferent 
      neurons during colitis and was not involved in BDNF action in the DRG. Our 
      results suggest that colon-to-bladder sensory cross-sensitization is regulated by 
      specific signal transduction initiated by the up-regulation of BDNF in the DRG.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Xia, Chunmei
AU  - Xia C
AD  - Department of Physiology and Biophysics, School of Medicine, Virginia 
      Commonwealth University, Richmond, VA, USA.
FAU - Shen, Shanwei
AU  - Shen S
AD  - Department of Physiology and Biophysics, School of Medicine, Virginia 
      Commonwealth University, Richmond, VA, USA.
FAU - Hashmi, Fiza
AU  - Hashmi F
AD  - Department of Physiology and Biophysics, School of Medicine, Virginia 
      Commonwealth University, Richmond, VA, USA.
FAU - Qiao, Li-Ya
AU  - Qiao LY
AD  - Department of Physiology and Biophysics, School of Medicine, Virginia 
      Commonwealth University, Richmond, VA, USA. Electronic address: 
      liya.qiao@vcuhealth.org.
LA  - eng
GR  - R01 DK077917/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20151211
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - CREB-Binding Protein/metabolism
MH  - Colitis/chemically induced/*pathology
MH  - Disease Models, Animal
MH  - Ganglia, Spinal/*pathology
MH  - Male
MH  - Mice, Knockout
MH  - Neurons/drug effects/*physiology
MH  - Phospholipase C gamma/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/*physiology
MH  - Trinitrobenzenesulfonic Acid/toxicity
MH  - Up-Regulation/drug effects/physiology
MH  - Urinary Bladder/innervation
PMC - PMC4903097
MID - NIHMS746922
OTO - NOTNLM
OT  - BDNF
OT  - Bladder
OT  - Colon
OT  - Cross-sensitization
OT  - Signal transduction
COIS- The Authors disclose no conflicts
EDAT- 2016/10/25 06:00
MHDA- 2017/05/10 06:00
PMCR- 2017/11/01
CRDT- 2015/12/22 06:00
PHST- 2015/07/09 00:00 [received]
PHST- 2015/11/14 00:00 [revised]
PHST- 2015/12/10 00:00 [accepted]
PHST- 2016/10/25 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2015/12/22 06:00 [entrez]
PHST- 2017/11/01 00:00 [pmc-release]
AID - S0014-4886(15)30133-3 [pii]
AID - 10.1016/j.expneurol.2015.12.006 [doi]
PST - ppublish
SO  - Exp Neurol. 2016 Nov;285(Pt B):126-135. doi: 10.1016/j.expneurol.2015.12.006. 
      Epub 2015 Dec 11.