Vagal nerve stimulation rapidly activates brain-derived neurotrophic factor receptor TrkB in rat brain.
Vagal nerve stimulation rapidly activates brain-derived neurotrophic factor receptor TrkB in rat brain.
复制标题
DOI：
10.1371/journal.pone.0034844
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Frazer A
中科院分区：
文献类型：
--
作者：
Furmaga H;Carreno FR;Frazer A
迷走神经刺激(VNS)已被批准用于难治性抑郁症。许多抗抑郁药可增加脑源性神经营养因子(BDNF)在脑内的表达，或通过磷酸化激活其受体TrkB。目前还没有关于VNS是否也会导致TrkB磷酸化的研究。免疫印迹法检测急性和慢性给予迷走神经后大鼠海马区TrkB的磷酸化状态。将VNS的急性效应与氟西汀或地塞帕明(DMI)的急性效应进行比较，将其慢性效应与舍曲林或DMI的慢性效应进行比较。所有的治疗，无论是急性的还是慢性的，都显著提高了海马区TrkB上酪氨酸705和816的磷酸化水平。然而，只有VNS增加了酪氨酸515的磷酸化，急性和慢性给药都引起了这种效应。非特异性酪氨酸激酶抑制剂K252a可阻断急性VNS引起的三种酪氨酸的磷酸化。经VNS急性处理后，Y515的下游效应分子Akt和ERK也被磷酸化，而DMI不引起这种作用。VNS会迅速激活TrkB的磷酸化，并且这种作用会随着时间的推移而持续。VNS诱导的酪氨酸515的磷酸化与标准抗抑郁药物的作用不同。
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.
登录
查看更多内容
DOI：
10.1083/jcb.150.6.1423
发表时间：
2000-09-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Du J;Feng L;Yang F;Lu B
通讯作者：
Lu B
影响因子：
10.6
作者：
Karege, F;Bondolfi, G;Bertschy, G
通讯作者：
Bertschy, G
DOI：
10.1073/pnas.0509494102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Berghuis, P;Dobszay, MB;Harkany, T
通讯作者：
Harkany, T
影响因子：
3.3
作者：
KASE, H;IWAHASHI, K;MATSUDA, Y
通讯作者：
MATSUDA, Y
DOI：
10.1124/jpet.106.104166
发表时间：
2006-08-01
影响因子：
3.5
作者：
Dorr, Adrienne E.;Debonnel, Guy
通讯作者：
Debonnel, Guy