PMID- 24303055
OWN - NLM
STAT- MEDLINE
DCOM- 20141001
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - In vivo regulation of brain-derived neurotrophic factor in dorsal root ganglia is 
      mediated by nerve growth factor-triggered Akt activation during cystitis.
PG  - e81547
LID - 10.1371/journal.pone.0081547 [doi]
LID - e81547
AB  - The role of brain-derived neurotrophic factor (BDNF) in sensory hypersensitivity 
      has been suggested; however the molecular mechanisms and signal transduction that 
      regulate BDNF expression in primary afferent neurons during visceral inflammation 
      are not clear. Here we used a rat model of cystitis and found that the mRNA and 
      protein levels of BDNF were increased in the L6 dorsal root ganglia (DRG) in 
      response to bladder inflammation. BDNF up-regulation in the L6 DRG was triggered 
      by endogenous nerve growth factor (NGF) because neutralization of NGF with a 
      specific NGF antibody reduced BDNF levels during cystitis. The neutralizing NGF 
      antibody also subsequently reduced cystitis-induced up-regulation of the 
      serine/threonine kinase Akt activity in L6 DRG. To examine whether the 
      NGF-induced Akt activation led to BDNF up-regulation in DRG in cystitis, we found 
      that in cystitis the phospho-Akt immunoreactivity was co-localized with BDNF in 
      L6 DRG, and prevention of the endogenous Akt activity in the L6 DRG by inhibition 
      of phosphoinositide 3-kinase (PI3K) with a potent inhibitor LY294002 reversed 
      cystitis-induced BDNF up-regulation. Further study showed that application of NGF 
      to the nerve terminals of the ganglion-nerve two-compartmented preparation 
      enhanced BDNF expression in the DRG neuronal soma; which was reduced by 
      pre-treatment of the ganglia with the PI3K inhibitor LY294002 and wortmannin. 
      These in vivo and in vitro experiments indicated that NGF played an important 
      role in the activation of Akt and subsequent up-regulation of BDNF in the sensory 
      neurons in visceral inflammation such as cystitis.
FAU - Qiao, Li-Ya
AU  - Qiao LY
AD  - Department of Physiology and Biophysics, Virginia Commonwealth University School 
      of Medicine, Richmond, Virginia, United States of America.
FAU - Yu, Sharon J
AU  - Yu SJ
FAU - Kay, Jarren C
AU  - Kay JC
FAU - Xia, Chun-Mei
AU  - Xia CM
LA  - eng
GR  - R01 DK077917/DK/NIDDK NIH HHS/United States
GR  - DK077917/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131126
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cystitis/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Enzyme Activation
MH  - Ganglia, Spinal/*metabolism
MH  - Male
MH  - Nerve Growth Factor/antagonists & inhibitors/*metabolism
MH  - Phosphatidylinositol 3-Kinases
MH  - Protein Binding
MH  - Protein Transport
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Signal Transduction
PMC - PMC3841217
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/05 06:00
MHDA- 2014/10/02 06:00
PMCR- 2013/11/26
CRDT- 2013/12/05 06:00
PHST- 2013/07/15 00:00 [received]
PHST- 2013/10/24 00:00 [accepted]
PHST- 2013/12/05 06:00 [entrez]
PHST- 2013/12/05 06:00 [pubmed]
PHST- 2014/10/02 06:00 [medline]
PHST- 2013/11/26 00:00 [pmc-release]
AID - PONE-D-13-29102 [pii]
AID - 10.1371/journal.pone.0081547 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 26;8(11):e81547. doi: 10.1371/journal.pone.0081547. 
      eCollection 2013.