PMID- 19332029
OWN - NLM
STAT- MEDLINE
DCOM- 20090814
LR  - 20091119
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1273
DP  - 2009 Jun 1
TI  - Acceleration of methylmercury-induced cell death of rat cerebellar neurons by 
      brain-derived neurotrophic factor in vitro.
PG  - 155-62
LID - 10.1016/j.brainres.2009.03.035 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor 
      (NGF) family and has been shown to promote neuronal survival and contribute to 
      neural development. Although methylmercury, a neurotoxin, induces the cell death 
      of neurons in vitro, there is little information regarding the effects of 
      neurotrophins on the methylmercury-induced cell death of neurons. In the present 
      study, we investigated the effect of BDNF on methylmercury-induced cell death in 
      a primary culture of rat cerebellar granular cells. BDNF increased the viability 
      of the cultured cells when treated alone, but unexpectedly accelerated the cell 
      death induced by administration of methylmercury. Among other growth factors 
      tested, only neurotrophin-4 (NT-4) demonstrated a similar acceleration of 
      methylmercury-induced cell death. The cell death-accelerating effect of BDNF was 
      inhibited by a BDNF-neutralizing antibody or a MAPK inhibitor. To determine 
      whether the effect of BDNF occurs via TrkB, a receptor of BDNF and NT-4, we 
      investigated the effects of BDNF and methylmercury in a TrkB transformant of rat 
      neuroblastoma B35 cells. The methylmercury-induced cell death of the TrkB 
      transformant was accelerated by BDNF, while that of the mock transformant was 
      not. These results indicate that BDNF accelerates methylmercury-induced cell 
      death via TrkB, at least in vitro, and suggest that BDNF and TrkB may also 
      contribute to the sensitivity of neurons to methylmercury toxicity.
FAU - Sakaue, Motoharu
AU  - Sakaue M
AD  - Department of Anatomy II, School of Veterinary Medicine, Azabu University, 
      1-17-71 Fuchinobe, Sagamihara 229-8501, Japan. sakaue@azabu-u.ac.jp
FAU - Mori, Naoko
AU  - Mori N
FAU - Makita, Misato
AU  - Makita M
FAU - Fujishima, Kana
AU  - Fujishima K
FAU - Hara, Shuntaro
AU  - Hara S
FAU - Arishima, Kazuyoshi
AU  - Arishima K
FAU - Yamamoto, Masako
AU  - Yamamoto M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090328
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antibodies)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Methylmercury Compounds)
RN  - 0 (Neurotoxins)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism/*toxicity
MH  - Cell Death/drug effects/physiology
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Central Nervous System/*drug effects/metabolism/pathology
MH  - Drug Synergism
MH  - Enzyme Inhibitors/pharmacology
MH  - MAP Kinase Signaling System/drug effects/physiology
MH  - Mercury Poisoning, Nervous System/*metabolism/physiopathology
MH  - Methylmercury Compounds/*toxicity
MH  - Nerve Degeneration/chemically induced/metabolism/physiopathology
MH  - Neurons/*drug effects/metabolism/pathology
MH  - Neurotoxins/*toxicity
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/drug effects/genetics/metabolism
EDAT- 2009/04/01 09:00
MHDA- 2009/08/15 09:00
CRDT- 2009/04/01 09:00
PHST- 2009/01/27 00:00 [received]
PHST- 2009/03/13 00:00 [revised]
PHST- 2009/03/15 00:00 [accepted]
PHST- 2009/04/01 09:00 [entrez]
PHST- 2009/04/01 09:00 [pubmed]
PHST- 2009/08/15 09:00 [medline]
AID - S0006-8993(09)00600-3 [pii]
AID - 10.1016/j.brainres.2009.03.035 [doi]
PST - ppublish
SO  - Brain Res. 2009 Jun 1;1273:155-62. doi: 10.1016/j.brainres.2009.03.035. Epub 2009 
      Mar 28.