PMID- 19393251
OWN - NLM
STAT- MEDLINE
DCOM- 20091001
LR  - 20220331
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 57
IP  - 1
DP  - 2009 Jul
TI  - BDNF-TrkB signaling pathway mediates the induction of epileptiform activity 
      induced by a convulsant drug cyclothiazide.
PG  - 49-59
LID - 10.1016/j.neuropharm.2009.04.007 [doi]
AB  - 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 are 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, pre-treatment 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.
FAU - Wang, Yun
AU  - Wang Y
AD  - Institutes of Brain Science and State Key Laboratory for Medical Neurobiology, 
      Fudan University, Shanghai 200032, China. yunwang@fudan.edu.cn
FAU - Qi, Jin-Shun
AU  - Qi JS
FAU - Kong, Shuzhen
AU  - Kong S
FAU - Sun, Yajie
AU  - Sun Y
FAU - Fan, Jing
AU  - Fan J
FAU - Jiang, Min
AU  - Jiang M
FAU - Chen, Gong
AU  - Chen G
LA  - eng
GR  - R21 NS054858/NS/NINDS NIH HHS/United States
GR  - R21 NS054858-01A2/NS/NINDS NIH HHS/United States
GR  - R21 NS054858-02/NS/NINDS NIH HHS/United States
GR  - NS054858/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090422
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Antibodies)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Benzothiadiazines)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - P71U09G5BW (cyclothiazide)
SB  - IM
MH  - Action Potentials/drug effects
MH  - Analysis of Variance
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Antihypertensive Agents/*pharmacology
MH  - Benzothiadiazines/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Carbazoles/pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Epilepsy/*chemically induced/pathology/*physiopathology
MH  - Hippocampus/pathology
MH  - In Vitro Techniques
MH  - Indole Alkaloids/pharmacology
MH  - Male
MH  - Neurons/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/immunology/*metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - Time Factors
PMC - PMC2733837
MID - NIHMS128124
EDAT- 2009/04/28 09:00
MHDA- 2009/10/02 06:00
PMCR- 2010/07/01
CRDT- 2009/04/28 09:00
PHST- 2008/09/30 00:00 [received]
PHST- 2009/04/03 00:00 [revised]
PHST- 2009/04/14 00:00 [accepted]
PHST- 2009/04/28 09:00 [entrez]
PHST- 2009/04/28 09:00 [pubmed]
PHST- 2009/10/02 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - S0028-3908(09)00110-5 [pii]
AID - 10.1016/j.neuropharm.2009.04.007 [doi]
PST - ppublish
SO  - Neuropharmacology. 2009 Jul;57(1):49-59. doi: 10.1016/j.neuropharm.2009.04.007. 
      Epub 2009 Apr 22.