Intrastriatal quinolinic acid injections protect against 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal system.
We tested the effect of intrastriatal quinolinic acid (QA) injections 2 weeks before subsequent intrastriatal injections of 6-hydroxydopamine (6-OHDA). Levels of DA and its metabolites were measured 2 days and 21 days after lesioning the dopaminergic nigrostriatal system with 6-OHDA. Intrastriatal 6-OHDA injections in the absence of prior treatment of QA significantly decreased dopamine (DA) and its metabolite levels in striatum but not in substantia nigra at day 2, and in striatum and substantia nigra at day 21, a clear indication of a time-dependent retrograde axonal degeneration of substantia nigra cell bodies. Intrastriatal QA injections 2 weeks before subsequent intrastriatal injection of 6-OHDA partially prevented the 6-OHDA-depleting effect on DA and its metabolite levels in both striatum and substantia nigra 21 days after 6-OHDA injection. However, no statistically significant differences were found between QA + 6-OHDA- and 6-OHDA-treated animals at day 2. Our results suggest that intrastriatal QA injections partially prevent the naturally-occurring retrograde axonal degeneration of substantia nigra cell bodies caused by 6-OHDA, and illustrate a target-derived interaction between dopaminergic nerve endings and cell bodies. We suggest that the protective effect found in the QA-injected animals against the neurotoxic action of 6-OHDA is mediated by neurotrophic agents released by activated astroglia.
Venero
J L
JL
Departamento de Bioquímica, Bromatología y Toxicología, Facultad de Farmacia, Universidad de Sevilla, Spain.
Romero-Ramos
M
M
Revuelta
M
M
Machado
A
A
Cano
J
J
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D005260:Female; D007267:Injections; D018696:Neuroprotective Agents / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology* / Q000633:toxicity; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology
D018696:Neuroprotective Agents; D016627:Oxidopamine; D017378:Quinolinic Acid; D004298:Dopamine