Vagal nerve stimulation rapidly activates brain-derived neurotrophic factor receptor TrkB in rat brain

Havan Furmaga, Flavia Regina Carreno, Alan Frazer

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere34844
JournalPLoS One
Volume7
Issue number5
DOIs
StatePublished - May 1 2012

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trkB Receptor
Vagus Nerve Stimulation
Phosphorylation
neurotrophins
Rats
Brain
nerve tissue
phosphorylation
brain
receptors
rats
tyrosine
Desipramine
Tyrosine
antidepressants
hippocampus
Antidepressive Agents
Hippocampus
Sertraline
Treatment-Resistant Depressive Disorder

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Vagal nerve stimulation rapidly activates brain-derived neurotrophic factor receptor TrkB in rat brain. / Furmaga, Havan; Carreno, Flavia Regina; Frazer, Alan.

In: PLoS One, Vol. 7, No. 5, e34844, 01.05.2012.

Research output: Contribution to journalArticle

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