PMID- 23500004
OWN - NLM
STAT- MEDLINE
DCOM- 20140620
LR  - 20131004
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 56
DP  - 2013 Sep
TI  - 7,8-Dihydroxyflavone leads to survival of cultured embryonic motoneurons by 
      activating intracellular signaling pathways.
PG  - 18-28
LID - S1044-7431(13)00025-0 [pii]
LID - 10.1016/j.mcn.2013.02.007 [doi]
AB  - Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family and 
      a ligand for the tropomyosin-receptor kinase B (TrkB), mediates neuronal 
      survival, differentiation, and synaptic plasticity. However, BDNF is not used to 
      treat neurodegenerative diseases because of its poor pharmacokinetic profile, 
      side effects, and absence of survival properties in clinical trials. 
      Consequently, alternative approaches such as TrkB receptor agonist application 
      are gaining importance. 7,8-Dihydroxyflavone (7,8-DHF), a member of the flavonoid 
      family, has been described as a robust TrkB receptor agonist in hippocampal 
      neurons. Nevertheless, the influence of 7,8-DHF on motoneurons, one of the main 
      targets of BDNF in vivo, is so far unknown. Therefore, we investigated the impact 
      of 7,8-DHF treatment on primary cultured mouse motoneurons. Indeed, we found an 
      activation of the TrkB receptor. Moreover, 7,8-DHF application promotes survival 
      and neurite growth of cultured motoneurons and these effects appear 
      dose-dependent. To investigate the PI3K/AKT and MAPK pathway activation in 
      7,8-DHF treated motoneurons, we developed a high-density culture system of 
      primary mouse motoneurons. Analysis of both pathways demonstrated a PI3K/AKT but 
      not MAPK pathway activation in cultured motoneurons. This is in contrast to 
      previously published reports about BDNF-mediated activation of TrkB. The lack of 
      MAPK pathway activation is also in contrast to what has been found for 
      hippocampal neurons that indeed show MAPK activation after 7,8-DHF treatment. The 
      ability of 7,8-DHF to imitate BDNF function in motoneurons by using Trk receptor 
      signaling would provide a new approach for the treatment of motoneuron diseases, 
      but needs a more detailed analysis of the activation profile of 7,8-DHF.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Tsai, Teresa
AU  - Tsai T
AD  - Institute for Cellmorphology and molecular Neurobiology, Group for molecular Cell 
      biology, Universitaetsstrasse 150, Ruhr-University Bochum, Germany.
FAU - Klausmeyer, Alice
AU  - Klausmeyer A
FAU - Conrad, Rebecca
AU  - Conrad R
FAU - Gottschling, Christine
AU  - Gottschling C
FAU - Leo, Markus
AU  - Leo M
FAU - Faissner, Andreas
AU  - Faissner A
FAU - Wiese, Stefan
AU  - Wiese S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130314
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (6,7-dihydroxyflavone)
RN  - 0 (Flavones)
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Growth Processes
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Flavones/*pharmacology
MH  - Hippocampus/cytology/embryology
MH  - *MAP Kinase Signaling System
MH  - Mice
MH  - Motor Neurons/*drug effects/metabolism/physiology
MH  - Neurites/drug effects/metabolism/physiology
MH  - Neuroprotective Agents/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, trkB/agonists/metabolism
MH  - Spinal Cord/cytology/embryology
OTO - NOTNLM
OT  - 7,8-DHF
OT  - 7,8-dihydroxyflavone
OT  - ALS
OT  - Agonist
OT  - BDNF
OT  - E
OT  - Flavonoids
OT  - KRH
OT  - Krebs-Ringer solution
OT  - MN
OT  - Neurotrophin
OT  - PBS
OT  - PFA
OT  - SMA
OT  - Spinal cord
OT  - TBS
OT  - Tris-buffered saline
OT  - TrkB
OT  - TrkB receptor
OT  - amyotrophic lateral sclerosis
OT  - brain derived neurotrophic factor
OT  - embryonic day
OT  - motoneurons
OT  - p75 Neurotrophin receptor
OT  - p75(NTR)
OT  - paraformaldehyde
OT  - phosphate-buffered saline
OT  - spinal muscular atrophy
OT  - tropomyosin-related kinase receptor tyrosine kinase B
EDAT- 2013/03/19 06:00
MHDA- 2014/06/21 06:00
CRDT- 2013/03/19 06:00
PHST- 2012/09/04 00:00 [received]
PHST- 2013/01/25 00:00 [revised]
PHST- 2013/02/27 00:00 [accepted]
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2014/06/21 06:00 [medline]
AID - S1044-7431(13)00025-0 [pii]
AID - 10.1016/j.mcn.2013.02.007 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2013 Sep;56:18-28. doi: 10.1016/j.mcn.2013.02.007. Epub 2013 
      Mar 14.