AMPA-induced dark cell degeneration is associated with activation of caspases in pyramidal neurons of the rat hippocampus.
Various neurons in the central nervous system (CNS) exhibit selective vulnerability to AMPA-induced delayed neurotoxicity known as dark cell degeneration. Hippocampal pyramidal neurons in the CA1 and CA3 regions display such vulnerability that encompasses morphological changes including cytoplasmic and nuclear condensation, neuronal shrinkage, formation of cytoplasmic vacuoles, and general failure of physiology. The present study was undertaken to ascertain the potential involvement of initiator (caspase-9) and executor (caspase-3) caspases in AMPA-receptor-induced dark cell degeneration in pyramidal neurons. Immunohistochemical analyses revealed that immunoreactivity of the active form of caspase-9 and -3 was increased in pyramidal neurons in CA1 and CA3 regions of the hippocampus following AMPA (100 microM). Elevated levels of active caspase-9 immunoreactivity generally preceded elevations in active caspase-3 immunoreactivity. The pan caspase inhibitor FK011 effectively attenuated AMPA-induced dark cell degeneration in both CA1 and CA3 regions. Collectively, the data suggest a role for these caspases in mediating AMPA-induced toxicity in pyramidal neurons of the rat hippocampus.
Coles
Jennifer
J
Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA.
Oomman
Sowmini K
SK
Henne
William M
WM
Bliss
Richard M
RM
Hoffman
Trenton C
TC
Finckbone
VelvetLee
V
Strahlendorf
Howard
H
Strahlendorf
Jean
J
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D002452:Cell Count; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology*; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000201:enzymology; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity*
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; C413643:benzyloxycarbonyl-aspartyl(O-methyl)fluoromethane; D001224:Aspartic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D020169:Caspases