title: AMPA-induced excitotoxicity increases nuclear levels of CAD, endonuclease G, and acinus and induces chromatin condensation in rat hippocampal pyramidal neurons.
abstract: Programmed cell death has been linked to AMPA-receptor-mediated excitotoxicity in pyramidal neurons of the hippocampus. The intent of this study was to investigate the roles of caspase-dependent and independent nuclear death-related factors in mediating AMPA-induced nuclear changes in PyNs by use of immunohistochemistry and transmission electron microscopy (TEM). Data indicate increases in the nuclear levels of caspase-activated acinus and DNase and Endonuclease G (a caspase-independent endonuclease) in CA1 and CA3 PyN nuclei with different temporal patterns following an AMPA-insult. Hoechst staining and TEM confirm AMPA-induced chromatin condensation. The presence of active acinus in nuclei suggests it mediates chromatin condensation. Interestingly, a DNA fragmentation labeling protocol showed that there was no chromatin cleavage up to 90 min after AMPA-insult. Overall, we conclude that: 1) AMPA-induced excitotoxicity increases nuclear immunoreactivity of pro-death enzymes from multiple programmed cell death pathways, 2) differential chromatin condensation patterns occur between CA1 and CA3, and 3) there is no chromatin cleavage within our experimental timeframe.
authors.affiliation: Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Henne
authors.forename: S
authors.initials: S
authors.lastname: Oomman
authors.forename: J
authors.initials: J
authors.lastname: Attridge
authors.forename: V
authors.initials: V
authors.lastname: Finckbone
authors.forename: P
authors.initials: P
authors.lastname: Coates
authors.forename: R
authors.initials: R
authors.lastname: Bliss
authors.forename: H
authors.initials: H
authors.lastname: Strahlendorf
authors.forename: J
authors.initials: J
authors.lastname: Strahlendorf
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D020287:In Situ Nick-End Labeling; D009687:Nuclear Proteins / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
chemical_list: D001562:Benzimidazoles; D002843:Chromatin; D009687:Nuclear Proteins; C447680:hoechst 32258; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; C109663:caspase-activated deoxyribonuclease; C052391:endonuclease G