Validity of a quantitative technique to study striatal dopaminergic neurodegeneration by in vivo microdialysis.
The development of a technique that allows the direct quantitative study of the damage produced by a toxin on a specific neurotransmitter system is very important. For that, we have used the microdialysis technique to validate a method to study the specific drug's toxicity on dopaminergic (DAergic) striatal terminals. We perfused different MPP(+) and 6-hydroxydopamine (6-OHDA) concentrations, with different toxicity for DAergic terminals, 24 h after the implantation of the microdialysis probe (day 1). One day later (day 2), MPP(+) was perfused through the microdialysis probe and DA extracellular output measured. We hypothesize that the amount of extracellular dopamine (DA) obtained on day 2 is directly proportional to the neurotoxic damage produced on day 1. To corroborate this hypothesis tyrosine hydroxylase (TH) immunohistochemistry was also carried out on day 2. There was a clear correlation index between the amount of DA measured after MPP(+) perfusion and the lack of TH immunoreactivity measured as the radius of the area showing decrease in TH immunoreactivity around the cannula. These results show the possibility to measure DAergic remaining terminals after a toxic drug exposure by in vivo MPP(+) perfusion. The possibility to extend this neurotoxic study to another neurotransmitter systems is suggested.
Santiago
M
M
Departamento de Bioquímica, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.
Machado
A
A
Cano
J
J
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013223:Statistics as Topic; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D009498:Neurotoxins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine