title: Apolipoprotein E protects against NMDA excitotoxicity.
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.
authors.affiliation: Multidisciplinary Neuroprotection Laboratory, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Aono
authors.forename: Yoonki
authors.initials: Y
authors.lastname: Lee
authors.forename: Elfrida R
authors.initials: ER
authors.lastname: Grant
authors.forename: Robert A
authors.initials: RA
authors.lastname: Zivin
authors.forename: Robert D
authors.initials: RD
authors.lastname: Pearlstein
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Bennett
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
mesh_terms: 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
chemical_list: D001057:Apolipoproteins E; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016202:N-Methylaspartate; D002118:Calcium