PMID- 10686066
OWN - NLM
STAT- MEDLINE
DCOM- 20000329
LR  - 20131121
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 161
IP  - 2
DP  - 2000 Feb
TI  - Differential effects of BDNF, ADNF9, and TNFalpha on levels of NMDA receptor 
      subunits, calcium homeostasis, and neuronal vulnerability to excitotoxicity.
PG  - 442-52
AB  - Calcium influx through N-methyl-d-aspartate (NMDA) receptors can result in 
      neuronal apoptosis or necrosis and may play a pivotal role in neuronal death in 
      many different neurodegenerative diseases. In the present study we employed 
      primary neuronal cultures and three different excitoprotective factors, 
      brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophic factor 
      (ADNF9), and tumor necrosis factor alpha (TNFalpha), to elucidate the mechanisms 
      whereby trophic factors modify the excitotoxic process. Neurons pretreated with 
      BDNF exhibited increased levels of the NMDA receptor subunits NR1 and NR2A, which 
      was associated with increased calcium responses to NMDA and vulnerability to 
      excitotoxic necrosis and reduced vulnerability to apoptosis. ADNF9 and TNFalpha 
      suppressed calcium responses to glutamate and protected neurons against both 
      excitotoxic necrosis and apoptosis, but had no effect on levels of NMDA receptor 
      subunits. Inhibition of phosphorylation and DNA binding of NF-kappaB, by H7 and 
      kappaB decoy DNA, respectively, suggest that the excitotoxic-modulating actions 
      of BDNF are mediated by kinases, while those of ADNF9 and TNFalpha are mediated 
      by both kinases and the transcription factor NF-kappaB. Our data show that, 
      whereas BDNF increases neuronal responses to glutamate while ADNF9 and TNFalpha 
      decrease the same, all three protect against excitotoxic apoptosis.
CI  - Copyright 2000 Academic Press.
FAU - Glazner, G W
AU  - Glazner GW
AD  - Sanders-Brown Research Center on Aging, Department of Anatomy, University of 
      Kentucky, Lexington, 40536, Kentucky, USA.
FAU - Mattson, M P
AU  - Mattson MP
LA  - eng
GR  - NRSA467305/NR/NINR NIH HHS/United States
GR  - NS29001/NS/NINDS NIH HHS/United States
GR  - NS35253/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NR2A NMDA receptor)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotoxins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Brain/cytology/*physiology
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Calcium/*metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dizocilpine Maleate/pharmacology
MH  - Embryo, Mammalian
MH  - Glutamic Acid/pharmacology
MH  - Homeostasis
MH  - Kinetics
MH  - Necrosis
MH  - Nerve Tissue Proteins/*pharmacology
MH  - Neurons/cytology/drug effects/*physiology
MH  - Neurotoxins/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
EDAT- 2000/02/25 09:00
MHDA- 2000/04/01 09:00
CRDT- 2000/02/25 09:00
PHST- 2000/02/25 09:00 [pubmed]
PHST- 2000/04/01 09:00 [medline]
PHST- 2000/02/25 09:00 [entrez]
AID - S0014-4886(99)97242-4 [pii]
AID - 10.1006/exnr.1999.7242 [doi]
PST - ppublish
SO  - Exp Neurol. 2000 Feb;161(2):442-52. doi: 10.1006/exnr.1999.7242.