Age dependence of striatal neuronal death caused by mitochondrial dysfunction.

Several lines of evidence point to a decline in mitochondrial efficiency with age. The relationship between age and sensitivity to Huntington disease-like neuronal death in the striatum induced by the mitochondrial inhibitor 3-nitropropionic acid (3-NP) was examined. 3-NP has been shown to cause degeneration of striatum, hippocampus, and thalamus in rat and of caudate-putamen in humans. We administered single doses of 3-NP intraperitoneally to rats of various ages. Animals older than 4 months exhibited a far greater susceptibility to striatal neurotoxicity and mortality compared with younger animals. These results are discussed in the context of age-dependent metabolic impairment, which may be a key factor in the etiology of neurodegenerative disorders such as Huntington's disease and Alzheimer's disease.