Age-dependent neurotoxicity of striatal lesions produced by aminooxyacetic acid: quantitative in vitro 1H NMR spectroscopic studies.
Aminooxyacetic acid, a potent inhibitor of the mitochondrial malate-aspartate shunt, was used to assess the role of mitochondrial energy metabolism in damaged brain of rats of different age groups. Three age groups--juvenile (< 1 month), young adult (3-4 months), and adult (7 months)--were subjected to examine the age-related aminooxyacetic acid effect. We measured the absolute concentrations of metabolites in perchloric acid extracts of rat striatum after intraperitoneal administration of aminooxyacetic acid using 1H NMR spectroscopy. Among aminooxyacetic acid-treated groups, a twofold increase of GABA concentration was observed in juveniles and young adults, and a threefold elevation of GABA level was observed in adults, whereas there were no significant differences of alanine and glutamate levels in all three aminooxyacetic acid-treated groups as compared with the age-matched controls. Statistically significant decreases of N-acetylaspartate, glutamine, and creatine levels were detected in treated adults. A statistically significant elevation of lactate concentration was found in the adult treated group. These data have demonstrated that the impairment of energy metabolism in rat striatum induced by aminooxyacetic acid can be revealed by quantitative in vitro 1H NMR spectroscopy and that aminooxyacetic acid produces age-dependent striatal abnormalities.
Chang
C
C
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Jang
T
T
D000375:Aging / Q000502:physiology*; D000409:Alanine / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007773:Lactates; D005973:Glutamine; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine; D000409:Alanine; D005998:Glycine