Abstract
Preclinical and clinical evidence implicates a role for endogenous apolipoprotein E in modifying the response of the brain to focal and global ischemia. To investigate whether apoE modulates the neuronal response to glutamate excitotoxicity, we exposed primary neuronal glial cultures and a neuronal cell line to biologically relevant concentrations of apolipoprotein E prior to NMDA exposure. In both of these paradigms, apolipoprotein E exerted partial protective effects. At neuroprotective concentrations, however, apolipoprotein E failed to block NMDA-induced calcium influx to the same magnitude as the NMDA receptor antagonist MK-801. These results suggest that one mechanism by which apolipoprotein E modifies the central nervous system response to ischemia may be by reducing glutamate-induced excitotoxicity.
| Original language | English |
|---|---|
| Pages (from-to) | 214-220 |
| Number of pages | 7 |
| Journal | Neurobiology of Disease |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 19 2002 |
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Keywords
- Apolipoprotein E
- Calcium influx
- Cell culture
- Cerebral ischemia
- Excitotoxicity
- Neuroprotection
- NMDA
- RAP
ASJC Scopus subject areas
- Neurology
Cite this
Apolipoprotein E protects against NMDA excitotoxicity. / Aono, Mitsuo; Lee, Yoonki; Grant, Elfrida R.; Zivin, Robert A.; Pearlstein, Robert D.; Warner, David S.; Bennett, Ellen R.; Laskowitz, Daniel T.
In: Neurobiology of Disease, Vol. 11, No. 1, 19.12.2002, p. 214-220.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Apolipoprotein E protects against NMDA excitotoxicity
AU - Aono, Mitsuo
AU - Lee, Yoonki
AU - Grant, Elfrida R.
AU - Zivin, Robert A.
AU - Pearlstein, Robert D.
AU - Warner, David S.
AU - Bennett, Ellen R.
AU - Laskowitz, Daniel T.
PY - 2002/12/19
Y1 - 2002/12/19
N2 - Preclinical and clinical evidence implicates a role for endogenous apolipoprotein E in modifying the response of the brain to focal and global ischemia. To investigate whether apoE modulates the neuronal response to glutamate excitotoxicity, we exposed primary neuronal glial cultures and a neuronal cell line to biologically relevant concentrations of apolipoprotein E prior to NMDA exposure. In both of these paradigms, apolipoprotein E exerted partial protective effects. At neuroprotective concentrations, however, apolipoprotein E failed to block NMDA-induced calcium influx to the same magnitude as the NMDA receptor antagonist MK-801. These results suggest that one mechanism by which apolipoprotein E modifies the central nervous system response to ischemia may be by reducing glutamate-induced excitotoxicity.
AB - Preclinical and clinical evidence implicates a role for endogenous apolipoprotein E in modifying the response of the brain to focal and global ischemia. To investigate whether apoE modulates the neuronal response to glutamate excitotoxicity, we exposed primary neuronal glial cultures and a neuronal cell line to biologically relevant concentrations of apolipoprotein E prior to NMDA exposure. In both of these paradigms, apolipoprotein E exerted partial protective effects. At neuroprotective concentrations, however, apolipoprotein E failed to block NMDA-induced calcium influx to the same magnitude as the NMDA receptor antagonist MK-801. These results suggest that one mechanism by which apolipoprotein E modifies the central nervous system response to ischemia may be by reducing glutamate-induced excitotoxicity.
KW - Apolipoprotein E
KW - Calcium influx
KW - Cell culture
KW - Cerebral ischemia
KW - Excitotoxicity
KW - Neuroprotection
KW - NMDA
KW - RAP
UR - http://www.scopus.com/inward/record.url?scp=0036453085&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036453085&partnerID=8YFLogxK
U2 - 10.1006/nbdi.2002.0541
DO - 10.1006/nbdi.2002.0541
M3 - Article
VL - 11
SP - 214
EP - 220
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 1
ER -