Quinolinate neurotoxicity and glutamatergic structures.
Neurotoxic properties of quinolinic acid following intracerebroventricular application were investigated in the hippocampal formation of 12- and 30-day-old rats. Quinolinic acid neurodegenerative potency was found to depend on the survival time, the dose applied and the developmental stage of the animal. Pretreatment with kynurenic acid and ketamine as well as the transection of the perforant path were noted to protect major parts of the hippocampal cell layers from quinolinic acid-induced degenerative effects. The results are interpreted in view of a putative dependence of quinolinic acid neurotoxicity on the presence of established synaptic, in particular glutamatergic, processes which play a major role in the hippocampal formation and mature during the first postnatal weeks. For comparison, we studied local effects of quinolinic acid on superior cervical and dorsal root ganglia in which glutamate inputs obviously do not occur; no signs of neuronal vulnerability were seen.
Keilhoff
G
G
Institute of Biology, Medical Academy of Magdeburg, G.D.R.
Wolf
G
G
Stastný
F
F
Schmidt
W
W
D000367:Age Factors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D007276:Injections, Intraventricular; D007649:Ketamine / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D011725:Pyridines / Q000633:toxicity*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D005971:Glutamates; D009498:Neurotoxins; D011725:Pyridines; D011805:Quinolinic Acids; D018698:Glutamic Acid; D007649:Ketamine; D017378:Quinolinic Acid; D007736:Kynurenic Acid