Chronic intoxication with 3-nitropropionic acid in rats induces the loss of striatal dopamine terminals without affecting nigral cell viability.
3-Nitropropionic acid (3NP) is a succinate dehydrogenase inhibitor allowing the generation of animal models of Huntington's disease. In the present study, we found that a 5-day continuous chronic infusion of 3NP produces loss of [3H]mazindol binding and tyrosine hydroxylase (TH) immunoreactivity in the striatal area of degeneration. This loss of dopamine terminals was not due to a loss of nigral neurons since the expression of TH as well as the number of TH-expressing neurons remained unaltered in the substantia nigra of rats treated by 3NP. This suggests that the 3NP-induced dopamine terminal loss is secondarily related to the striatal degeneration andlor to a direct effect of 3NP on striatal terminals and not to a primary effect on nigral cells.
Blum
David
D
Laboratory of Neurophysiology, Université Libre de Bruxelles-Erasme, CP601, 808 route de Lennik, 1070 Brussels, Belgium. dablum@ulb.ac.be
Galas
Marie-Christine
MC
Cuvelier
Laetitia
L
Schiffmann
Serge N
SN
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001665:Binding Sites; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008454:Mazindol / Q000378:metabolism; D009574:Nitro Compounds; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D011422:Propionates / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D014316:Tritium / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000959:Antihypertensive Agents; D007527:Isoenzymes; D009574:Nitro Compounds; D011422:Propionates; D012333:RNA, Messenger; D014316:Tritium; D008454:Mazindol; D002237:Carbohydrate Dehydrogenases; C104557:sorbose dehydrogenase; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C015392:3-nitropropionic acid; D004298:Dopamine