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

• Published in: PloS one 2012-05, Vol.7 (5), p.e34844-e34844
• Main Authors: Furmaga, Havan, Carreno, Flavia Regina, Frazer, Alan
• Format: Article
• Language: English
• Subjects: Acute effects; Adrenergic Uptake Inhibitors - pharmacology; AKT protein; Animals; Antidepressants; Biology; Blotting, Western; Brain; Brain - drug effects; Brain - metabolism; Brain-derived neurotrophic factor; Brain-derived neurotrophic factor receptors; Carbazoles - pharmacology; Chronic effects; Depression; Depression (Mood disorder); Desipramine; Desipramine - pharmacology; Drugs; Enzyme inhibitors; Enzyme Inhibitors - pharmacology; Extracellular signal-regulated kinase; Fluoxetine; Fluoxetine - pharmacology; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Indole Alkaloids - pharmacology; Kinases; Male; Medicine; Mental depression; Phosphorylation; Phosphorylation - drug effects; Protein-tyrosine kinase; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Receptor, trkB - metabolism; Rodents; Serotonin Uptake Inhibitors - pharmacology; Sertraline; Stimulation; Time Factors; Tricyclic antidepressants; TrkB receptors; Tyrosine; Tyrosine - metabolism; Vagus nerve; Vagus Nerve - drug effects; Vagus Nerve - physiology; Vagus Nerve Stimulation - methods; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0034844

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. 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. 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. 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.