Abstract
Huntington’s disease (HD) is an inherited, autosomal dominant, neurodegenerative disorder characterized by involuntary choreiform movements, progressive cognitive decline, psychiatric manifestations, and a neuronal degeneration primarily affecting the striatum. Neuropathological examination indicates that striatal y-amino butyric acid (GABA)ergic projecting neurons are preferentially affected, whereas striatal interneurons are relatively spared (1). The gene responsible for the disease (IT15) has been cloned, and the molecular abnormality has been identified as an expanded polyglutamine tract in the N-terminal region of a protein of unknown function, named huntingtin (2). Recent studies showed that huntingtin interacts with a number of proteins; some of them with well identified functions. Thus, it has been suggested that alterations in glycolysis, vesicle trafficking, or apoptosis may play a role in the physiopathology of HD (3–6). Other data derived from positron emission tomography, magnetic resonance spectroscopy, and postmortem biochemistry, showing evidences for a defect in succinate oxidation, have suggested the potential implication of a primary impairment of mitochondrial energy metabolism (6). Based on this mitochondrial hypothesis, phenotypic animal models of HD have been elaborated both in rodents and nonhuman primates, employing a chronic blockade of succinate oxidation by systemic administration of the mitochondrial toxin, 3-nitropropionic acid (3-NP) (7–11). Historically, initial experimental studies in nonhuman primates used unilateral striatal injections of glutamatergic agonists, such as quinolinic and ibotenic acid, to induce abnormal movements. More recently, experimental studies used a systemic injection of 3-NP in nonhuman primates to induce both choreiform and dystonic movements associated with bilateral selective striatal lesions ressembling those observed in HD (12).
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Palfi, S., Brouillet, E., Condé, F., Hantraye, P. (2003). Induction and Reversal of Cognitive Deficits in a Primate Model of Huntington’s Disease. In: Bédard, MA., Agid, Y., Chouinard, S., Fahn, S., Korczyn, A.D., Lespérance, P. (eds) Mental and Behavioral Dysfunction in Movement Disorders. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-326-2_12
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DOI: https://doi.org/10.1007/978-1-59259-326-2_12
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