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.
Bossi
S R
SR
Neuroregeneration Laboratory, McLean Hospital, Belmont, MA 02178.
Simpson
J R
JR
Isacson
O
O
D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000473:pathology*; D006651:Histocytochemistry; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009574:Nitro Compounds; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D009574:Nitro Compounds; D011422:Propionates; D000110:Acetylcholinesterase; C015392:3-nitropropionic acid