PMID- 22563458
OWN - NLM
STAT- MEDLINE
DCOM- 20120921
LR  - 20230921
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Vagal nerve stimulation rapidly activates brain-derived neurotrophic factor 
      receptor TrkB in rat brain.
PG  - e34844
LID - 10.1371/journal.pone.0034844 [doi]
LID - e34844
AB  - BACKGROUND: Vagal nerve stimulation (VNS) has been approved for 
      treatment-resistant depression. Many antidepressants increase expression of 
      brain-derived neurotrophic factor (BDNF) in brain or activate, via 
      phosphorylation, its receptor, TrkB. There have been no studies yet of whether 
      VNS would also cause phosphorylation of TrkB. METHODS: Western blot analysis was 
      used to evaluate the phosphorylation status of TrkB in the hippocampus of rats 
      administered VNS either acutely or chronically. Acute effects of VNS were 
      compared with those caused by fluoxetine or desipramine (DMI) whereas its chronic 
      effects were compared with those of sertraline or DMI. RESULTS: All treatments, 
      given either acutely or chronically, significantly elevated phosphorylation of 
      tyrosines 705 and 816 on TrkB in the hippocampus. However, only VNS increased the 
      phosphorylation of tyrosine 515, with both acute and chronic administration 
      causing this effect. Pretreatment with K252a, a nonspecific tyrosine kinase 
      inhibitor, blocked the phosphorylation caused by acute VNS at all three 
      tyrosines. Downstream effectors of Y515, namely Akt and ERK, were also 
      phosphorylated after acute treatment with VNS, whereas DMI did not cause this 
      effect. CONCLUSION: VNS rapidly activates TrkB phosphorylation and this effect 
      persists over time. VNS-induced phosphorylation of tyrosine 515 is distinct from 
      the effect of standard antidepressant drugs.
FAU - Furmaga, Havan
AU  - Furmaga H
AD  - Department of Pharmacology, University of Texas Health Science Center, San 
      Antonio, Texas, United States of America.
FAU - Carreno, Flavia Regina
AU  - Carreno FR
FAU - Frazer, Alan
AU  - Frazer A
LA  - eng
GR  - R01 MH082933/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120501
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 42HK56048U (Tyrosine)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - TG537D343B (Desipramine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - Brain/drug effects/*metabolism
MH  - Carbazoles/pharmacology
MH  - Desipramine/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fluoxetine/pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Indole Alkaloids/pharmacology
MH  - Male
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/*metabolism
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
MH  - Time Factors
MH  - Tyrosine/*metabolism
MH  - Vagus Nerve/drug effects/physiology
MH  - Vagus Nerve Stimulation/*methods
PMC - PMC3341395
COIS- Competing Interests: Drs. Furmaga and Carreno have no competing interests to 
      declare. Previously, Dr. Frazer received financial compensation as a consultant 
      for Cyberonics, Inc. and had also obtained grant support from them for a 
      preclinical study. This does not alter the authors' adherence to all the PLoS ONE 
      policies on sharing data and materials.
EDAT- 2012/05/09 06:00
MHDA- 2012/09/22 06:00
PMCR- 2012/05/01
CRDT- 2012/05/08 06:00
PHST- 2011/08/09 00:00 [received]
PHST- 2012/03/08 00:00 [accepted]
PHST- 2012/05/08 06:00 [entrez]
PHST- 2012/05/09 06:00 [pubmed]
PHST- 2012/09/22 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - PONE-D-11-15560 [pii]
AID - 10.1371/journal.pone.0034844 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e34844. doi: 10.1371/journal.pone.0034844. Epub 2012 May 1.