Quantifiable bradykinesia, gait abnormalities and Huntington's disease-like striatal lesions in rats chronically treated with 3-nitropropionic acid

Neuroscience
M C GuyotE Brouillet

Abstract

Impairment in energy metabolism is thought to be involved in the aetiology of Huntington's disease. In line with this hypothesis, chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid to rats and monkeys produces selective striatal lesions similar to Huntington's disease. The present study examined whether rats treated with varying regimen of 3-nitropropionic acid could present motor abnormalities reminiscent of Huntington's disease symptomatology, correlated with Huntington's disease specific striatal symptomatology. Subacute 3-nitropropionic acid treatment (15 mg/kg per day intraperitoneally for 10 days) produced dramatic motor symptoms associated with extensive neuronal loss and gliosis in the lateral striatum as well as severe hippocampal degeneration in 50% of the cases. In contrast, chronic 3-nitropropionic acid treatment (10 mg/kg per day subcutaneously for one month) led to more subtle excitotoxic-like lesions, selective for the dorsolateral striatum and more closely resembling Huntington's disease striatal pathology. Animals with these Huntington's disease-like lesions showed spontaneous motor symptoms including mild dystonia, bradykinesia and gait abnormalities, which were barely detectable ...Continue Reading

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