Indirect glutamate neurotoxicity.
Indirect glutamate toxicity can be demonstrated by exposing dissociated rat hippocampal cultures to the media of the same culture transiently exposed (1 min) to glutamate (0.5 mM). The toxicity was maximum when the media was collected 5 min after the glutamate exposure. While the primary glutamate toxicity was attenuated by ionotropic glutamate receptor antagonists, the transferred, indirect toxicity was unaffected by the same antagonists. The changes in nuclear morphology indicated chromatin condensation and nuclear fragmentation in both primary and transferred toxicity. The stain for DNA damage by TUNEL method also revealed cells staining positive in both primary and transferred glutamate toxicity. These observations demonstrate that glutamate-induced neurotoxicity can be propagated to the uninjured cells by an unknown toxin released into the extracellular space. This neurotoxin induced both apoptosis and necrosis in cultured rat hippocampal cells.
Yoon
K W
KW
Department of Surgery, St. Louis University Health Science Center, MO 63110-0250, USA.
Fuse
T
T
Shah
P T
PT
Nguyen
S
S
Klein
M L
ML
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000502:physiology; D046508:Culture Techniques; D053938:DNA Fragmentation; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000506:poisoning*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009336:Necrosis; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione