The organotypic tissue culture model of corticostriatal system used for examining amino acid neurotoxicity and its antagonism: studies on kainic acid, quinolinic acid and (-) 2-amino-7-phosphonoheptanoic acid.
Organotypic cultures of caudate nucleus and frontal cerebral cortex, either alone or in combination with each other, have been used to evaluate and compare the neurotoxic effects of two dicarboxylic amino acids, kainic acid (KA) and the tryptophan metabolite quinolinic acid (QUIN). Both of these agents can induce specific post-synaptic degeneration in cultures in which a complement of well-developed mature synapses exists. The neurotoxic effects of QUIN can be blocked by the synthetic anti-convulsant agent (-)2-amino-7-phosphonoheptanoic acid [( -]APH), but neurotoxicity of KA cannot. These studies support the candicacy of QUIN as an endogenous neurotoxin with properties similar to KA. Furthermore, the studies demonstrate the usefulness of the organotypic nerve tissue culture model as a research tool for examining certain neurodegenerative phenomena and for identifying neurotoxic amino acids as well as compounds which may antagonize amino acid neurotoxicity.
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000344:Afferent Pathways / Q000187:drug effects; D000596:Amino Acids / Q000633:toxicity*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects*; D007608:Kainic Acid / Q000633:toxicity*; D008854:Microscopy, Electron; D008959:Models, Neurological; D009410:Nerve Degeneration / Q000187:drug effects; D011725:Pyridines / Q000633:toxicity*; D011759:Pyrrolidines / Q000633:toxicity*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000596:Amino Acids; D011725:Pyridines; D011759:Pyrrolidines; D011805:Quinolinic Acids; D015763:2-Amino-5-phosphonovalerate; D017378:Quinolinic Acid; C031231:2-amino-7-phosphonoheptanoic acid; D007608:Kainic Acid