TY - JOUR
T1 - Activation of signaling pathways downstream of the brain-derived neurotrophic factor receptor, TrkB, in the rat brain by vagal nerve stimulation and antidepressant drugs
AU - Carreno, Flavia Regina
AU - Frazer, Alan
PY - 2014/2
Y1 - 2014/2
N2 - Vagal nerve stimulation (VNS) has been approved for treatment resistant depression (TRD) by the Food and Drug Administration (FDA) since 2005. However, the cellular and molecular targets responsible for its effects are still not characterized. Previously, chronic administration of VNS to rats was found to phosphorylate tyrosine 515 on TrkB, the neurotrophin receptor, whereas traditional antidepressants did not do this. In the present study, Western blot analysis was used to characterize activation due to phosphorylation in the hippocampus of down-stream pathways linked to specific key tyrosine residues on TrkB (namely Y816 and Y515) after either acute or chronic administration of VNS and traditional antidepressant drugs. Chronic administration of VNS caused phosphorylation of effectors linked to Y 515; namely Akt, ERK and p70S6 kinase, but this was not produced by either desipramine or sertraline. All the treatments, when given chronically, caused phosphorylation of the transcription factor, CREB. Acute administration of all the treatments also caused phosphorylation of PLCγ1 but this was not maintained with chronic treatment. Further research is required to determine what role, if any, activation of down-stream targets of Y515 plays in the behavioural effects of VNS.
AB - Vagal nerve stimulation (VNS) has been approved for treatment resistant depression (TRD) by the Food and Drug Administration (FDA) since 2005. However, the cellular and molecular targets responsible for its effects are still not characterized. Previously, chronic administration of VNS to rats was found to phosphorylate tyrosine 515 on TrkB, the neurotrophin receptor, whereas traditional antidepressants did not do this. In the present study, Western blot analysis was used to characterize activation due to phosphorylation in the hippocampus of down-stream pathways linked to specific key tyrosine residues on TrkB (namely Y816 and Y515) after either acute or chronic administration of VNS and traditional antidepressant drugs. Chronic administration of VNS caused phosphorylation of effectors linked to Y 515; namely Akt, ERK and p70S6 kinase, but this was not produced by either desipramine or sertraline. All the treatments, when given chronically, caused phosphorylation of the transcription factor, CREB. Acute administration of all the treatments also caused phosphorylation of PLCγ1 but this was not maintained with chronic treatment. Further research is required to determine what role, if any, activation of down-stream targets of Y515 plays in the behavioural effects of VNS.
KW - Antidepressants
KW - TrkB
KW - desipramine
KW - sertraline
KW - vagal nerve stimulation
UR - http://www.scopus.com/inward/record.url?scp=84891770617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891770617&partnerID=8YFLogxK
U2 - 10.1017/S1461145713000977
DO - 10.1017/S1461145713000977
M3 - Article
C2 - 24103847
AN - SCOPUS:84891770617
SN - 1461-1457
VL - 17
SP - 247
EP - 258
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
IS - 2
ER -