Deprenyl enhances the striatal neuronal damage produced by quinolinic acid.
We have tested the effect of deprenyl on the neurotoxicity induced by the injection of quinolinic acid within the striatum. Deprenyl was unable to prevent these quinolinic acid-induced damages, but enhanced the loss of several gamma-aminobutyric acid (GABA) positive subpopulations, the loss of the astroglial population and the activation of microglia produced by quinolinic acid. These effects are produced by deprenyl potentiation of dopamine actions since dopamine depletion produced by previous injection of the dopaminergic toxin 6-hydroxydopamine within the medial forebrain bundle overcomes deprenyl effects and the involvement of dopamine in the quinolinic acid-induced toxicity in striatum. In these conditions, quinolinic acid toxic action in striatum is significantly lower and similar in the animals treated with or without deprenyl. All these data justify why deprenyl worsen some pathological signals of disorders involving excitotoxicity. This also may be involved in other secondary effects described for deprenyl.
de Pablos
Rocío M
RM
Departamento de Bioquímica, Bromatología, Toxicología y Medicina Legal. Facultad de Farmacia, Universidad de Sevilla, Spain. C/Prof. García González 2, 41012-Sevilla, Spain.
Herrera
Antonio J
AJ
Tomás-Camardiel
Mayka
M
Machado
Alberto
A
Cano
Josefina
J
D000818:Animals; D000978:Antiparkinson Agents / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D064026:Calbindins; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000378:metabolism / Q000494:pharmacology; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism; D012642:Selegiline / Q000378:metabolism*; D013565:Sympatholytics / Q000378:metabolism / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000978:Antiparkinson Agents; D015415:Biomarkers; D064026:Calbindins; D007527:Isoenzymes; D010320:Parvalbumins; D017448:Receptors, Dopamine D2; D064030:S100 Calcium Binding Protein G; D013565:Sympatholytics; D012642:Selegiline; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D017378:Quinolinic Acid; D004298:Dopamine