Abstract
In several neurological disorders including Alzheimer's disease, abnormal accumulations of cytoskeleton-associated proteins manifest as neurofibrillary tangles (NFTs) in vulnerable brain regions. Antibodies recognizing tau (5E2 and Alz-50) and ubiquitin epitopes in NFTs were used to examine the influence of glutamate and Ca2+ influx on antigen expression in cultured rat hippocampal neurons. Glutamate caused the degeneration of a subpopulation of pyramidal neurons, which exhibited increased immunostaining with all three antibodies. Subtoxic levels of glutamate also increased 5E2 and Alz-50 antigen levels in a subpopulation of neurons, particularly in the distal regions of the axons. Both glutamate-induced degeneration and increases in tau and ubiquitin immunostaining were prevented by removal of extracellular Ca2+ Increased immunostaining was also induced by Ca2+ ionophore A23187 or elevated levels of extracellular K+. The antigenic changes occurred within 1 hr of exposure to glutamate or A23187 and were not prevented by the protein synthesis inhibitor cycloheximide. These data indicate that Ca2+ influx caused by glutamate can lead to modifications of extant proteins similar to those seen in NFTs.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 105-117 |
| Number of pages | 13 |
| Journal | Neuron |
| Volume | 4 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1990 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
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Antigenic changes similar to those seen in neurofibrillary tangles are elicited by glutamate and Ca2+ influx in cultured hippocampal neurons. / Mattson, Mark P.
In: Neuron, Vol. 4, No. 1, 1990, p. 105-117.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antigenic changes similar to those seen in neurofibrillary tangles are elicited by glutamate and Ca2+ influx in cultured hippocampal neurons
AU - Mattson, Mark P.
PY - 1990
Y1 - 1990
N2 - In several neurological disorders including Alzheimer's disease, abnormal accumulations of cytoskeleton-associated proteins manifest as neurofibrillary tangles (NFTs) in vulnerable brain regions. Antibodies recognizing tau (5E2 and Alz-50) and ubiquitin epitopes in NFTs were used to examine the influence of glutamate and Ca2+ influx on antigen expression in cultured rat hippocampal neurons. Glutamate caused the degeneration of a subpopulation of pyramidal neurons, which exhibited increased immunostaining with all three antibodies. Subtoxic levels of glutamate also increased 5E2 and Alz-50 antigen levels in a subpopulation of neurons, particularly in the distal regions of the axons. Both glutamate-induced degeneration and increases in tau and ubiquitin immunostaining were prevented by removal of extracellular Ca2+ Increased immunostaining was also induced by Ca2+ ionophore A23187 or elevated levels of extracellular K+. The antigenic changes occurred within 1 hr of exposure to glutamate or A23187 and were not prevented by the protein synthesis inhibitor cycloheximide. These data indicate that Ca2+ influx caused by glutamate can lead to modifications of extant proteins similar to those seen in NFTs.
AB - In several neurological disorders including Alzheimer's disease, abnormal accumulations of cytoskeleton-associated proteins manifest as neurofibrillary tangles (NFTs) in vulnerable brain regions. Antibodies recognizing tau (5E2 and Alz-50) and ubiquitin epitopes in NFTs were used to examine the influence of glutamate and Ca2+ influx on antigen expression in cultured rat hippocampal neurons. Glutamate caused the degeneration of a subpopulation of pyramidal neurons, which exhibited increased immunostaining with all three antibodies. Subtoxic levels of glutamate also increased 5E2 and Alz-50 antigen levels in a subpopulation of neurons, particularly in the distal regions of the axons. Both glutamate-induced degeneration and increases in tau and ubiquitin immunostaining were prevented by removal of extracellular Ca2+ Increased immunostaining was also induced by Ca2+ ionophore A23187 or elevated levels of extracellular K+. The antigenic changes occurred within 1 hr of exposure to glutamate or A23187 and were not prevented by the protein synthesis inhibitor cycloheximide. These data indicate that Ca2+ influx caused by glutamate can lead to modifications of extant proteins similar to those seen in NFTs.
UR - http://www.scopus.com/inward/record.url?scp=0025273543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025273543&partnerID=8YFLogxK
U2 - 10.1016/0896-6273(90)90447-N
DO - 10.1016/0896-6273(90)90447-N
M3 - Article
C2 - 1690014
AN - SCOPUS:0025273543
VL - 4
SP - 105
EP - 117
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -