Oxidative stress and neuronal DNA fragmentation mediate age-dependent vulnerability to the mitochondrial toxin, 3-nitropropionic acid, in the mouse striatum.
Oxidative stress is involved in the neuropathology of several neurodegenerative diseases and stroke, all of which are related to excitotoxicity. Age-dependent vulnerability is characteristic of these conditions. It is not clear whether apoptosis-related neuronal death is involved in age-dependent vulnerability to excitotoxicity. We evaluated whether apoptosis-related neuronal death after treatment with 3-nitropropionic acid (3-NP) is age-dependent in the mouse striatum. We have demonstrated that oxidative stress occurs early after 3-NP treatment and even more so in aged mice. DNA fragmentation with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and gel electrophoresis occurred in an age-dependent fashion. Expression of the DNA repair enzyme, apurinic/apyrimidinic endonuclease, was more attenuated in old mice. Therefore, these results suggest that oxidative stress induces age-dependent neuronal apoptosis in the mouse striatum after 3-NP treatment, which in turn produces an age-dependent vulnerability to 3-NP.
Kim
G W
GW
Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, California, USA.
Chan
P H
PH
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D009574:Nitro Compounds; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011422:Propionates / Q000633:toxicity*
D003574:Cytochrome c Group; D009498:Neurotoxins; D009574:Nitro Compounds; D009687:Nuclear Proteins; D011422:Propionates; C015392:3-nitropropionic acid