title: Peripheral type benzodiazepine binding sites are a sensitive indirect index of neuronal damage.
abstract: The effects of excitotoxic lesions on the neuronal marker enzymes choline acetyltransferase and glutamate decarboxylase and on the levels of 'peripheral type' benzodiazepine binding sites (PTBBS) (a putative glial marker) have been compared to see whether PTBBS provide a suitable if indirect quantitative index of neuronal damage. Intrastriatal injection of excitotoxic compounds provoked a dose-dependent increase in the levels of PTBBS. The potency order was the following: kainate greater than AMPA greater than N-methyl-D-aspartate (NMDA) greater than quisqualate. The maximal increases in this parameter were 400, 470, 320 and 210% for kainate (12 nmol), AMPA (100 nmol), NMDA (500 nmol) and quisqualate (250 nmol), respectively. 2-Amino-5-phosphonovalerate (100 nmol)--an antagonist of the NMDA receptor subtype--completely blocked the increase in PTBBS induced by NMDA (250 nmol), but was without effect against the other excitotoxins. Increases in binding levels were in general mirrored by a decrease in choline acetyltransferase and glutamate decarboxylase activity. However, PTBBS were a more sensitive indirect index of neuronal damage than neuronal enzymes because the alterations in binding were statistically significant at doses of excitotoxins lower than those causing a loss of marker enzymes. It is concluded that PTBBS are a suitable and sensitive means of detecting discrete neurotoxic changes and that its measurement will help in the study of other pathological and experimental models.
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001665:Binding Sites; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005968:Glutamate Decarboxylase; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate; D009410:Nerve Degeneration / Q000187:drug effects*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
chemical_list: D009498:Neurotoxins; D010069:Oxadiazoles; D011963:Receptors, GABA-A; D007051:Ibotenic Acid; D001224:Aspartic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D007608:Kainic Acid