title: Excitotoxicity is required for induction of oxidative stress and apoptosis in mouse striatum by the mitochondrial toxin, 3-nitropropionic acid.
abstract: Excitotoxicity is implicated in the pathogenesis of several neurologic diseases, such as chronic neurodegenerative diseases and stroke. Recently, it was reported that excitotoxicity has a relationship to apoptotic neuronal death, and that the mitochondrial toxin, 3-nitropropionic acid (3-NP), could induce apoptosis in the striatum. Although striatal lesions produced by 3-NP could develop through an excitotoxic mechanism, the exact relationship between apoptosis induction and excitotoxicity after 3-NP treatment is still not clear. The authors investigated the role of excitotoxicity and oxidative stress on apoptosis induction within the striatum after intraperitoneal injection of 3-NP. The authors demonstrated that removal of the corticostriatal glutamate pathway reduced superoxide production and apoptosis induction in the denervated striatum of decorticated mice after 3-NP treatment. Also, the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, prevented apoptosis in the striatum after 3-NP treatment for 5 days, whereas the non-NMDA receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline, was ineffective. The authors also evaluated the initial type of neuronal death by 3-NP treatment for different durations from 1 to 5 days. In early striatal damage, apoptotic neuronal death initially occurred after 3-NP treatment. Our data show that excitotoxicity related to oxidative stress initially induces apoptotic neuronal death in mouse striatum after treatment with 3-NP.
authors.affiliation: Department of Neurological Surgery, University of California, School of Medicine, San Francisco, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Kim
authors.forename: J C
authors.initials: JC
authors.lastname: Copin
authors.forename: M
authors.initials: M
authors.lastname: Kawase
authors.forename: S F
authors.initials: SF
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: G T
authors.initials: GT
authors.lastname: Gobbel
authors.forename: P H
authors.initials: PH
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003655:Decerebrate State / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects / Q000503:physiopathology; D009498:Neurotoxins / Q000378:metabolism*; D009574:Nitro Compounds; D018384:Oxidative Stress / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology* / Q000506:poisoning; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013481:Superoxides / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D013481:Superoxides; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate; D020169:Caspases; C015392:3-nitropropionic acid