PMID- 21276434
OWN - NLM
STAT- MEDLINE
DCOM- 20120312
LR  - 20131121
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1386
DP  - 2011 Apr 22
TI  - Tumor necrosis factor-alpha (TNF-alpha) augments AMPA-induced Purkinje neuron toxicity.
PG  - 1-14
LID - 10.1016/j.brainres.2011.01.059 [doi]
AB  - It is well recognized that exposure of neurons to excessive levels of the 
      excitatory neurotransmitter glutamate, termed glutamate excitotoxicity, 
      contributes to the damage and degeneration seen in many acute and chronic 
      neurological diseases. However, it is becoming increasingly evident that 
      inflammation also can play a role in certain neurodegenerative diseases and 
      inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha), may directly 
      interact with excitotoxic processes. In a postnatal rat cerebellar slice model, 
      we found that TNF-alpha exacerbated AMPA-induced excitotoxicity in Purkinje neurons 
      in a dose-dependent manner beyond the toxicity caused by AMPA alone. It also was 
      shown that combinations of TNF-alpha and AMPA increased the mean intracellular 
      activity of calpains, calcium-activated cysteine proteases that are known to 
      contribute to cell death in Purkinje neurons. Additionally, these combinations 
      augmented colbalt influx, a marker for calcium entry that selectively occurs 
      through calcium permeable AMPA receptors only. Pharmacologic blockade of calcium 
      permeable AMPA receptors with a specific antagonist, 1-naphthyl acetyl spermine 
      (NASPM), reversed the apparent increase in AMPA receptor calcium permeability 
      caused by TNF-alpha as measured by cobalt influx; caused a reduction in the Purkinje 
      neuron calpain activity; and reversed the enhanced neurodegeneration induced by 
      the combination of TNF-alpha and AMPA. From these studies we concluded that TNF-alpha 
      augmented AMPA-induced toxicity in Purkinje neurons by increasing intracellular 
      calcium flux through calcium permeable AMPA receptors, and this increase in 
      calcium was directly involved in enhanced activation of calpains and a greater 
      percentage of Purkinje neuron loss.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Bliss, Richard M
AU  - Bliss RM
AD  - Department of Cell Physiology and Molecular Biophysics, Texas Tech University 
      Health Sciences Center, Lubbock, TX 79430, USA.
FAU - Finckbone, Velvet Lee
AU  - Finckbone VL
FAU - Trice, Jacquelyn
AU  - Trice J
FAU - Strahlendorf, Howard
AU  - Strahlendorf H
FAU - Strahlendorf, Jean
AU  - Strahlendorf J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110126
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Inflammation Mediators)
RN  - 0 (Neurotoxins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Calcium/metabolism
MH  - Calcium Signaling/drug effects/physiology
MH  - Inflammation Mediators/*physiology
MH  - Nerve Degeneration/chemically induced/*metabolism/*pathology
MH  - Neurotoxins/agonists/toxicity
MH  - Organ Culture Techniques
MH  - Purkinje Cells/drug effects/*metabolism/*pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/*physiology
MH  - Up-Regulation/*physiology
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/agonists/*toxicity
EDAT- 2011/02/01 06:00
MHDA- 2012/03/13 06:00
CRDT- 2011/02/01 06:00
PHST- 2010/09/17 00:00 [received]
PHST- 2011/01/17 00:00 [revised]
PHST- 2011/01/19 00:00 [accepted]
PHST- 2011/02/01 06:00 [entrez]
PHST- 2011/02/01 06:00 [pubmed]
PHST- 2012/03/13 06:00 [medline]
AID - S0006-8993(11)00143-0 [pii]
AID - 10.1016/j.brainres.2011.01.059 [doi]
PST - ppublish
SO  - Brain Res. 2011 Apr 22;1386:1-14. doi: 10.1016/j.brainres.2011.01.059. Epub 2011 
      Jan 26.