Behavioral pathology induced by repeated systemic injections of 3-nitropropionic acid mimics the motoric symptoms of Huntington's disease.

Huntington's disease is a progressive neurodegenerative disorder associated with severe degeneration of basal ganglia neurons, especially the intrinsic neurons of the striatum, and characterized by involuntary abnormal choreiform movements and progressive dementia. With the discovery of the gene underlying HD, genetic therapy may be the next logical step towards finding a cure, but no such treatment is currently available. Animal models that closely mimic the neurobiological and clinical symptoms of the disease may offer an alternative approach for the development of new therapies. We report that systemic administration of 3-nitropropionic acid, an inhibitor of the mitochondrial citric acid cycle, results in a progressive locomotor deterioration resembling that of HD. We further demonstrate that manipulating the time course of 3-nitropropionic acid injections leads to sustained hyperactivity (early HD) or hypoactivity (advanced HD). These data suggest that this animal model can be used to test experimental treatments for HD across different stages of the disease.