Aminooxyacetic acid striatal lesions attenuated by 1,3-butanediol and coenzyme Q10.
We previously showed that intrastriatal administration of aminooxyacetic acid (AOAA) produces striatal lesions by a secondary excitotoxic mechanism associated with impairment of oxidative phosphorylation. In the present study, we show that and the specific complex I inhibitor rotenone produces a similar neurochemical profile in the striatum, consistent with an effect of AOAA on energy metabolism. Lesions produced by AOAA were dose-dependently blocked by MK-801, with complete protection against GABA and substance P depletions at a dose of 3 mg/kg. AOAA lesions were significantly attenuated by pretreatment with either 1,3-butanediol or coenzyme Q10, two compounds which are thought to improve energy metabolism. These results provide further evidence that AOAA produces striatal excitotoxic lesions as a consequence of energy depletion and they suggest therapeutic strategies which may be useful in neurodegenerative diseases.
Brouillet
E
E
Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114.
Henshaw
D R
DR
Schulz
J B
JB
Beal
M F
MF
D000625:Aminooxyacetic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002072:Butylene Glycols / Q000494:pharmacology*; D003067:Coenzymes; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D007657:Ketone Bodies / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors; D018377:Neurotransmitter Agents / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
D002072:Butylene Glycols; D003067:Coenzymes; D007657:Ketone Bodies; D008293:Malates; D018377:Neurotransmitter Agents; D012402:Rotenone; D014451:Ubiquinone; D000625:Aminooxyacetic Acid; D001224:Aspartic Acid; C028491:1,3-butylene glycol; D016291:Dizocilpine Maleate; C030298:malic acid; D016660:NAD(P)H Dehydrogenase (Quinone); C024989:coenzyme Q10