The 3-NP Model of Striatal Neurodegeneration.
The mitochondrial toxin 3-nitropropionic acid (3-NP) is an irreversible inhibitor of respiratory chain complex II. Chronic systemic administration of 3-NP to mice, rats, and non-human primates leads to preferential degeneration of the striatum, and produces motor and cognitive symptoms that are highly reminiscent of Huntington's disease (HD). HD is caused by a dominant inherited expansion of CAG repeats in the Huntington gene. Thus, many aspects of HD cannot be mimicked by 3-NP. However, recent research shows that mitochondrial defects and oxidative stress may play a key role in HD pathogenesis, further supporting the potential utility of the 3-NP model of striatal degeneration. First, a basic protocol to produce acute striatal lesions in rats using repeated intraperitoneal injection of 3-NP is described. Second, a more complex protocol that takes advantage of the use of osmotic minipumps to steadily release 3-NP leading to consistent lesions and motor symptoms in Lewis rats is presented.
Neurodegenerative Diseases Laboratory, URA2210, CEA, and CNRS, Molecular Imaging Research Center (MIRCen), I2BM, Life Science Division, Fontenay-aux-Roses, France.
Emmanuel
E
Brouillet
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000139:chemically induced / Q000473:pathology; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000473:pathology*; D009574:Nitro Compounds / Q000633:toxicity*; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley
D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid
Huntington's disease; chronic administration; mitochondria; neurodegeneration; striatum