Magnetic Resonance Imaging and Spectroscopy in Assessing 3-Nitropropionic Acid-Induced Brain Lesions: An Animal Model of Huntington's Disease = Wang-Tso Lee a And

Huntington's disease (HD) is an inherited neurodegenerative disease, in which there is progressive motor and cognitive deterioration, and for which the pathogenesis of neuronal death remains controversial. Mitochondrial toxins like 3- nitropropionic acid (3-NP) and malonate, functioning as the inhibitors of the complex II of mitochondrial respiratory chain, have been found to effectively induce specific behavioral changes and selective striatal lesions in rats and non-human primates mimicking those in HD. Furthermore, several kinds of transgenic mouse models of HD have been recently developed, and used in the development and assessment of novel treatments for HD. In the past, most studies evaluating the animal models for HD were based on histological changes or in vitro neuronal cultures. With the emergence of advanced magnetic resonance technologies, non- invasive magnetic resonance imaging (MRI) and spectroscopy provide more detail of cerebral alterations, including the changes of cerebral structure, function and metabolites. These studies support the hypothesis that mitochondrial dysfunction with increased excitation of N-methyl-D- aspartate (NMDA) receptors can replicate the neurobehavioral changes, selective brain injury and neurochemical alterations in HD. The present review focuses on our work as well as that of others regarding 3-NP-induced neurotoxicity and other animal models of HD. Using both conventional and advanced MRI and spectroscopy, we summarize the pathogenesis and possible therapeutic strategies in chemical and transgenic models of HD. The results show magnetic resonance techniques to be powerful techniques in the evaluation of pathogenesis and therapeutic intervention for both chemical and transgenic models of HD. (C) 2004 Elsevier Ltd. All rights reserved