PMID- 13678672
OWN - NLM
STAT- MEDLINE
DCOM- 20031029
LR  - 20191107
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 14
IP  - 1
DP  - 2003 Oct
TI  - TrkB mediates BDNF-induced potentiation of neuronal necrosis in cortical culture.
PG  - 110-9
AB  - In the present study, the signaling mechanisms underlying the effect of 
      brain-derived neurotrophic factor (BDNF) on neuronal necrosis were investigated. 
      Exposure of mature mouse cortical cultures (more than 10 days in vitro (DIV)) to 
      50-100 ng/ml BDNF for 48 h induced widespread neuronal necrosis that was 
      antioxidant-sensitive. This neuronal necrosis was blocked by the selective NMDA 
      antagonist MK-801, suggesting that prolonged BDNF exposure caused endogenous 
      levels of NMDA receptor activation to become excitotoxic. We examined whether the 
      p75(NTR) played a role in BDNF-induced neuronal death. However, p75(NTR) 
      expression was low in cultured cortical cells, and neutralizing antibodies to 
      p75(NTR) did not attenuate BDNF-triggered neuronal death. In contrast, trkB 
      antisense oligonucleotides and inhibitors of Trk tyrosine kinase blocked 
      BDNF-triggered neuronal death as well as BDNF potentiation of iron-induced 
      oxidative neuronal necrosis, suggesting a critical role for TrkB in this 
      phenomenon. Furthermore, BDNF did not potentiate neuronal necrosis in cortical 
      cultures prepared from embryonic TrkB-null mice. These results suggest that TrkB 
      plays an important role in BDNF-mediated neuronal necrosis.
FAU - Kim, Hyun-Jung
AU  - Kim HJ
AD  - National Creative Research Initiative Center for the Study of CNS Zinc, 
      University of Ulsan College of Medicine, Seoul 138-736, Korea.
FAU - Hwang, Jung Jin
AU  - Hwang JJ
FAU - Behrens, M Margarita
AU  - Behrens MM
FAU - Snider, B Joy
AU  - Snider BJ
FAU - Choi, Dennis W
AU  - Choi DW
FAU - Koh, Jae-Young
AU  - Koh JY
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Death/drug effects/physiology
MH  - Cells, Cultured
MH  - Cerebral Cortex/*drug effects/metabolism/pathology
MH  - Drug Synergism
MH  - Enzyme Inhibitors/pharmacology
MH  - Mice
MH  - Mice, Knockout
MH  - Necrosis
MH  - Neurons/*drug effects/metabolism/*pathology
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Receptor, trkB/deficiency/genetics/*physiology
EDAT- 2003/09/19 05:00
MHDA- 2003/10/30 05:00
CRDT- 2003/09/19 05:00
PHST- 2003/09/19 05:00 [pubmed]
PHST- 2003/10/30 05:00 [medline]
PHST- 2003/09/19 05:00 [entrez]
AID - S0969996103001037 [pii]
AID - 10.1016/s0969-9961(03)00103-7 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2003 Oct;14(1):110-9. doi: 10.1016/s0969-9961(03)00103-7.