Delayed excitotoxic neurodegeneration induced by excitatory amino acid agonists in isolated retina.
Evidence from in vitro studies suggests that excitotoxic neuronal degeneration can occur by either an acute or delayed mechanism. Studies of the acute mechanism in isolated chick embryo retina using histological methods indicate that this process is rapidly triggered by activation of glutamate receptors of either the N-methyl-D-aspartate (NMDA) or non-NMDA subtypes. The delayed mechanism, studied primarily in cortical and hippocampal cell cultures prepared from embryonic rodent brain, requires activation of NMDA receptors. In these cell culture systems, stimulation of non-NMDA receptors does not rapidly trigger delayed neuronal degeneration, or does so only indirectly, via activation of NMDA receptors secondary to glutamate release. To provide a more valid basis for comparison of these two mechanisms, we have modified the isolated chick embryo retina model to permit studies of delayed as well as acute excitotoxic neurodegeneration. Retinas maintained for 24 h exhibited no morphological or biochemical signs of damage. Retinal damage was assessed by measuring lactate dehydrogenase (LDH) present in the medium at various times after exposure to agonists and normalized to total LDH in each retina. Glutamate exposure (1 mM, 30 min) did not result in LDH release by the end of the exposure period, but LDH was released over the following 24 h. Briefer periods also led to substantial LDH release. Incubation in the presence of NMDA, or the non-NMDA agonists kainate (KA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), led rapidly to delayed LDH release.(ABSTRACT TRUNCATED AT 250 WORDS)
Romano
C
C
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Price
M T
MT
Olney
J W
JW
D000818:Animals; D016923:Cell Death; D002642:Chick Embryo; D018846:Excitatory Amino Acids / Q000819:agonists*; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009410:Nerve Degeneration; D009498:Neurotoxins / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*
D018846:Excitatory Amino Acids; D009498:Neurotoxins; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase