title: Systemic, but not intraparenchymal, administration of 3-nitropropionic acid mimics the neuropathology of Huntington's disease: a speculative explanation.
abstract: The mitochondrial toxin, 3-nitropropionic acid, has been introduced in recent years as a neurotoxin that can be administered systemically to model the many neurobehavioral correlates of Huntington's disease. In this update article, we discuss some of the many findings from experiments using the systemic 3-nitropropionic model, and provide some speculative explanations supporting this model over those utilizing conventional excitotoxins or direct intrastriatal application of 3-nitropropionic acid. We infer from our own studies and those of others that the slow process of neurodegeneration, probably through apoptotic mechanism, and the progressive locomotor dysfunctions (from dyskinesia to akinesia) inherent in Huntington's disease can be accomplished by chronic, low dose systemic administration of 3-nitropropionic acid in rodents as well as in non-human primates. This 3-nitropropionic acid model offers a new venue for investigating experimental treatment strategies for Huntington's disease.
authors.affiliation: Department of Anatomy and Cell Biology, F. Edward Hebert School of Medicine, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA. cborlong@usuhs.mil
authors.forename: C V
authors.initials: CV
authors.lastname: Borlongan
authors.forename: H
authors.initials: H
authors.lastname: Nishino
authors.forename: P R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000818:Animals; D006816:Huntington Disease / Q000139:chemically induced* / Q000473:pathology*; D007267:Injections; D017072:Neostriatum / Q000473:pathology; D009410:Nerve Degeneration / Q000187:drug effects; D009498:Neurotoxins / Q000008:administration & dosage* / Q000633:toxicity*; D009574:Nitro Compounds; D011422:Propionates / Q000008:administration & dosage* / Q000633:toxicity*; D051381:Rats
chemical_list: D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid