Specific lesions in the extrapyramidal system of the rat brain induced by 3-nitropropionic acid (3-NPA).
The irreversible mitochondrial toxin 3-nitropropionic acid (3-NPA) is a specific inhibitor of succinate dehydrogenase. We performed stereotaxic unilateral injections of 3-NPA into the nigrostriatal dopaminergic pathway in rats in order to examine its specific effects on the dopamine system. The 3-NPA-treated rats displayed unidirectional apomorphineinduced rotations, suggesting that 3-NPA selectively damages dopaminergic neurons when injected into the nigrostriatal pathway. In situ hybridization 7 weeks postinjection indicated a decrease in tyrosine hydroxylase (TH) mRNA to 30% of the noninjected side in the substantia nigra pars compacta (P < 0.05) and decreased to 62% of the noninjected side in the ventral tegmental area (VTA) (nonsignificant) of 3-NPA-lesioned rats. The number of TH mRNA positive cells showed statistically significant decreases in substantia nigra and VTA (P < 0.001) within the lesioned side. In contrast, expression of mRNAs encoding choline acetyltransferase, p75 low-affinity NGF receptor, neurotrophin tyrosine kinase receptors Trk and TrkB, and brain-derived neurotrophic factor showed neuronal sparing in several other regions of the brain. The results suggest that the nigrostriatal dopaminergic system might be selectively vulnerable to 3-NPA and demonstrate that it is possible to employ 3-NPA in a model of partial lesion of the nigrostriatal dopaminergic system resembling early stages of Parkinson's disease.
Pei
G
G
Department of Developmental Neuroscience, Uppsala University, Sweden.
Ebendal
T
T
D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D008297:Male; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism; D009574:Nitro Compounds; D016627:Oxidopamine / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D009414:Nerve Growth Factors; D009574:Nitro Compounds; D011422:Propionates; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; C015392:3-nitropropionic acid; D004298:Dopamine