PMID- 29092846
OWN - NLM
STAT- MEDLINE
DCOM- 20190715
LR  - 20201209
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 315
IP  - 1
DP  - 2018 Jul 1
TI  - BDNF overexpression in the bladder induces neuronal changes to mediate bladder 
      overactivity.
PG  - F45-F56
LID - 10.1152/ajprenal.00386.2017 [doi]
AB  - Elevated levels of brain-derived neurotrophic factor (BDNF) in urine of 
      overactive bladder (OAB) patients support the association of BDNF with OAB 
      symptoms, but the causality is not known. Here, we investigated the functionality 
      of BDNF overexpression in rat bladder following bladder wall transfection of 
      either BDNF or luciferase (luciferase) transgenes (10 microg). One week after 
      transfection, BDNF overexpression in bladder tissue and elevation of urine BDNF 
      levels were observed together with increased transcript of BDNF, its cognate 
      receptors (TrkB and p75(NTR)), and downstream PLCgamma isoforms in bladder. BDNF 
      overexpression can induce the bladder overactivity (BO) phenotype which is 
      demonstrated by the increased voiding pressure and reduced intercontractile 
      interval during transurethral open cystometry under urethane anesthesia. A role 
      for BDNF-mediated enhancement of prejunctional cholinergic transmission in BO is 
      supported by the significant increase in the atropine- and neostigmine-sensitive 
      component of nerve-evoked contractions and upregulation of choline 
      acetyltransferase, vesicular acetylcholine transporter, and transporter Oct2 and 
      -alpha1 receptors. In addition, higher expression of transient receptor channels 
      (TRPV1 and TRPA1) and pannexin-1 channels in conjunction with elevation of ATP 
      and neurotrophins in bladder and also in L6/S1 dorsal root ganglia together 
      support a role for sensitized afferent nerve terminals in BO. Overall, genomic 
      changes in efferent and afferent neurons of bladder induced by the overexpression 
      of BDNF per se establish a mechanistic link between elevated BDNF levels in urine 
      and dysfunctional voiding observed in animal models and in OAB patients.
FAU - Kashyap, Mahendra P
AU  - Kashyap MP
AD  - Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, 
      Pennsylvania.
FAU - Pore, Subrata K
AU  - Pore SK
AD  - Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, 
      Pennsylvania.
FAU - de Groat, William C
AU  - de Groat WC
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh School 
      of Medicine , Pittsburgh, Pennsylvania.
FAU - Chermansky, Christopher J
AU  - Chermansky CJ
AD  - Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, 
      Pennsylvania.
FAU - Yoshimura, Naoki
AU  - Yoshimura N
AD  - Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, 
      Pennsylvania.
FAU - Tyagi, Pradeep
AU  - Tyagi P
AUID- ORCID: 0000-0001-6586-4545
AD  - Department of Urology, University of Pittsburgh School of Medicine , Pittsburgh, 
      Pennsylvania.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20171101
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Receptors, Purinergic)
RN  - 136958-07-1 (Ngfr protein, rat)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cholinergic Fibers/*metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Nerve Tissue Proteins
MH  - Phospholipase C gamma/metabolism
MH  - Pressure
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/metabolism
MH  - Receptors, Growth Factor
MH  - Receptors, Nerve Growth Factor/metabolism
MH  - Receptors, Purinergic/metabolism
MH  - Synaptic Transmission
MH  - Transfection
MH  - Up-Regulation
MH  - Urinary Bladder/*innervation/*metabolism
MH  - Urinary Bladder, Overactive/genetics/*metabolism/physiopathology
MH  - *Urodynamics
PMC - PMC6087795
OTO - NOTNLM
OT  - afferent pathways
OT  - bladder overactivity
OT  - bladder transfection
OT  - brain-derived neurotrophic factor
OT  - efferent pathways
OT  - overactive bladder
EDAT- 2017/11/03 06:00
MHDA- 2019/07/16 06:00
PMCR- 2019/07/01
CRDT- 2017/11/03 06:00
PHST- 2017/11/03 06:00 [pubmed]
PHST- 2019/07/16 06:00 [medline]
PHST- 2017/11/03 06:00 [entrez]
PHST- 2019/07/01 00:00 [pmc-release]
AID - ajprenal.00386.2017 [pii]
AID - F-00386-2017 [pii]
AID - 10.1152/ajprenal.00386.2017 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2018 Jul 1;315(1):F45-F56. doi: 
      10.1152/ajprenal.00386.2017. Epub 2017 Nov 1.