Apolipoprotein E protects against NMDA excitotoxicity.
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.
Aono
Mitsuo
M
Multidisciplinary Neuroprotection Laboratory, Duke University Medical Center, Durham, North Carolina 27710, USA.
Lee
Yoonki
Y
Grant
Elfrida R
ER
Zivin
Robert A
RA
Pearlstein
Robert D
RD
Warner
David S
DS
Bennett
Ellen R
ER
Laskowitz
Daniel T
DT
D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D016202:N-Methylaspartate / Q000633:toxicity*; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins; D051381:Rats; D017207:Rats, Sprague-Dawley
D001057:Apolipoproteins E; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016202:N-Methylaspartate; D002118:Calcium