BDNF-TrkB signaling pathway mediates the induction of epileptiform activity induced by a convulsant drug cyclothiazide.
BDNF-TrkB signaling pathway mediates the induction of epileptiform activity induced by a convulsant drug cyclothiazide.
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BDNF-TrkB信号通路介导惊厥药物环噻嗪诱导的癫痫样活动
DOI：
10.1016/j.neuropharm.2009.04.007
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发表时间：
2009-07
影响因子：
4.7
通讯作者：
Chen, Gong
中科院分区：
文献类型：
--
作者：
Wang, Yun;Qi, Jin-Shun;Kong, Shuzhen;Sun, Yajie;Fan, Jing;Jiang, Min;Chen, Gong
脑源性神经营养因子（BDNF）及其受体TrkB在神经元发育和突触可塑性中起重要作用。最近，我们已经确定，环噻嗪（CTZ）是一种新的惊厥药物诱导强大的癫痫样活动在海马神经元在体外和体内。然而，CTZ这种惊厥作用的分子机制尚不清楚。在这里，我们研究了BDNF-TrkB信号通路在CTZ诱导癫痫样活动中的潜在作用。在麻醉大鼠中，CTZ剂量依赖性地诱导癫痫样活动，其特征在于群体尖峰、自发尖峰事件和同步癫痫样爆发的多个峰的进展。在脑室注射CTZ之前预先注射受体酪氨酸激酶抑制剂K252 a或TrkB受体特异性抗体显著抑制CTZ诱导的癫痫样活动。同样地，在培养的海马锥体神经元中，CTZ与K252 a或TrkB受体抗体一起预处理也抑制CTZ诱导的癫痫样活动。此外，我们证明，急性应用K252 a在海马培养抑制癫痫样爆发和动作电位放电。我们的结论是，激活BDNF-TrkB信号通路是从根本上重要的CTZ诱导癫痫样活动在体外和体内。
Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play an important function in neuronal development and synaptic plasticity. Recently we have established that cyclothiazide (CTZ) is a novel convulsant drug inducing robust epileptiform activity in hippocampal neurons both in vitro and in vivo. However, the molecular mechanisms underlying such convulsant action of CTZ is unknown. Here, we investigated potential roles of BDNF-TrkB signaling pathway in the CTZ-induction of epileptiform activity. In anaesthetized rats, CTZ dose-dependently induced epileptiform activity characterized by progressing of multiple peaks of population spikes, spontaneous spiking events, and synchronized epileptiform bursts. Pre-injection of a receptor tyrosine kinase inhibitor K252a or a specific antibody for TrkB receptors before intracerebroventricular injection of CTZ significantly suppressed the epileptiform activity induced by CTZ. Similarly, in cultured hippocampal pyramidal neurons, pretreatment with CTZ together with K252a or TrkB receptor antibody also inhibited the CTZ-induction of epileptiform activity. Furthermore, we demonstrated that acute application of K252a in hippocampal cultures inhibited epileptiform bursts and action potential firing. We conclude that activation of BDNF-TrkB signaling pathway is fundamentally important during the CTZ-induction of epileptiform activity both in vitro and in vivo.
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影响因子：
16.2
作者：
PARTIN, KM;PATNEAU, DK;BUONANNO, A
通讯作者：
BUONANNO, A
影响因子：
5.3
作者：
Balkowiec, A;Katz, DM
通讯作者：
Katz, DM
影响因子：
16.2
作者：
DIAMOND, JS;JAHR, CE
通讯作者：
JAHR, CE
DOI：
10.1073/pnas.2133370100
发表时间：
2003-10-28
影响因子：
11.1
作者：
Deng, LB;Chen, G
通讯作者：
Chen, G
影响因子：
16.2
作者：
Bellingham, MC;Walmsley, B
通讯作者：
Walmsley, B