SYSTEMIC, BUT NOT INTRAPARENCHYMAL, ADMINISTRATION OF 3-NITROPROPIONIC ACID MIMICS THE NEUROPATHOLOGY OF HUNTINGTONS-DISEASE - A SPECULATIVE EXPLANATION

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 experi ments using the systemic 3-nitropropionic model, and provide some spec ulative explanations supporting this model over those utilizing conven tional excitotoxins or direct intrastriatal application of 3-nitroprop ionic acid. We infer from our own studies and those of others that the slow process of neurodegeneration, probably through apoptotic mechani sm, and the progressive locomotor dysfunctions (from dyskinesia to aki nesia) 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 of fers a new venue for investigating experimental treatment strategies f or Huntington's disease. (C) 1997 Elsevier Science Ireland Ltd.