Neuronal damage in the albino rat: excitotoxin, microtubule inhibitor synergism.
Separate lines of investigation implicate excitotoxins or disruption of cytoskeletal architecture in the pathogenesis of human neurodegenerative disease. To assess the hypothesis that these neurotoxic mechanisms may have a synergistic effect, albino rats were given intrastriatal administrations of either the excitotoxin, kainic acid, or the microtubule inhibitor, colchicine, or both. Assessment of neuronal damage, either by loss of neurotransmitter metabolic enzyme activities or by histologic analysis, demonstrated synergism between the agents. Further, the synergism was still apparent with substitution of quinolinic acid, but not dimethyl kainate, for kainic acid, and Vinca alkaloids, but not lumicolchicine, for colchicine.
Cohen
M R
MR
Ensor Research Laboratory, William S. Hall Psychiatric Institute, Columbia, South Carolina.
Sridhara
N
N
McElveen
T S
TS
Gutman
R
R
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology*; D003078:Colchicine / Q000633:toxicity*; D004347:Drug Interactions; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008870:Microtubules / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D011699:Putamen / Q000187:drug effects / Q000473:pathology*; D011725:Pyridines / Q000633:toxicity*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D011725:Pyridines; D011805:Quinolinic Acids; D000110:Acetylcholinesterase; D017378:Quinolinic Acid; D007608:Kainic Acid; D003078:Colchicine