PMID- 24830751
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20140804
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 40
IP  - 3
DP  - 2014 Aug
TI  - The suppression of epileptiform discharges in cultured hippocampal neurons is 
      regulated via alterations in full-length tropomyosin-related kinase type B 
      receptors signalling activity.
PG  - 2564-75
LID - 10.1111/ejn.12620 [doi]
AB  - Epilepsy is a common neurological disease. Understanding the mechanisms of 
      epileptogenesis at the cellular and molecular levels may provide novel targets 
      for preventing this disorder. Brain-derived neurotrophic factor (BDNF) and its 
      receptor tropomyosin-related kinase type B (TrkB) are believed to be critical for 
      epileptogenesis. Previous studies have revealed possible changes in the 
      expression of full-length TrkB receptors (TrkB.FL) and truncated TrkB receptors 
      (TrkB.T) in neurodegenerative disorders. In this study, we investigated 
      alterations in TrkB receptor expression and TrkB signalling activity in a rat 
      hippocampal neuronal model of spontaneous recurrent epileptiform discharges 
      (SREDs) and the effects on the epileptiform discharges. To induce epileptiform 
      discharges, we established a model with Mg(2+) -free treatment. We found a 
      dramatic upregulation of TrkB.T and a decrease in TrkB.FL in the SREDs model. 
      Calpain contributed to the downregulation of TrkB.FL. The upregulation of TrkB.T 
      required transcription and translation activity. Furthermore, BDNF induced the 
      activation of TrkB.FL signalling. However, TrkB.FL signalling was inhibited in 
      the SREDs model. Although calpain inhibitors prevented a decrease in TrkB.FL, 
      they did not restrain the downregulation of TrkB.FL signalling activity in the 
      model. However, a SREDs model with a translation inhibitor prevented the increase 
      in TrkB.T and re-activated TrkB.FL signalling activity. Finally, we used 
      electrophysiology to observe that a downregulation of TrkB.T could relieve the 
      representative epileptiform discharges in the model. These results, taken 
      together, demonstrate that alterations in TrkB.FL signalling may be regulated via 
      TrkB.T receptors. Upregulation of TrkB.FL signalling suppresses epileptiform 
      discharges in the SREDs model.
CI  - (c) 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Xie, Wei
AU  - Xie W
AD  - School of Biomedical Engineering, Tianjin Medical University, Tianjin, China.
FAU - Song, Yi-Jun
AU  - Song YJ
FAU - Li, Dai
AU  - Li D
FAU - Pan, Li-Ping
AU  - Pan LP
FAU - Wu, Qiu-Jing
AU  - Wu QJ
FAU - Tian, Xin
AU  - Tian X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140515
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Isoenzymes)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.22.- (Calpain)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Calpain/metabolism
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Epilepsy/*metabolism
MH  - Female
MH  - Hippocampus/*metabolism/*physiopathology
MH  - Isoenzymes/metabolism
MH  - Male
MH  - Neurons/*metabolism/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/*genetics
MH  - *Signal Transduction
MH  - Up-Regulation
OTO - NOTNLM
OT  - TrkB receptor signalling
OT  - epilepsy
OT  - hippocampal neuron
OT  - rat
OT  - spontaneous recurrent epileptiform discharges
EDAT- 2014/05/17 06:00
MHDA- 2015/03/31 06:00
CRDT- 2014/05/17 06:00
PHST- 2014/01/05 00:00 [received]
PHST- 2014/04/01 00:00 [revised]
PHST- 2014/04/11 00:00 [accepted]
PHST- 2014/05/17 06:00 [entrez]
PHST- 2014/05/17 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
AID - 10.1111/ejn.12620 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2014 Aug;40(3):2564-75. doi: 10.1111/ejn.12620. Epub 2014 May 15.