BEHAVIORAL PATHOLOGY INDUCED BY REPEATED SYSTEMIC INJECTIONS OF 3-NITROPROPIONIC ACID MIMICS THE MOTORIC SYMPTOMS OF HUNTINGTONS-DISEASE

Huntington's disease is a progressive neurodegenerative disorder assoc iated with severe degeneration of basal ganglia neurons, especially th e intrinsic neurons of the striatum, and characterized by involuntary abnormal choreiform movements and progressive dementia. With the disco very of the gene underlying HD, genetic therapy may be the next logica l step towards finding a cure, but no such treatment is currently avai lable. Animal models that closely mimic the neurobiological and clinic al symptoms of the disease may offer an alternative approach for the d evelopment 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 tha t of HD. We further demonstrate that manipulating the time course of 3 -nitropropionic acid injections leads to sustained hyperactivity (earl y HD) or hypoactivity (advanced HD). These data suggest that this anim al model can be used to test experimental treatments for HD across dif ferent stages of the disease.