Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies in primates have shown that chronic systemic administration of the succinate dehydrogenase (SDH) inhibitor, 3-nitropropionic acid (3NP), replicates most of the motor, cognitive, and histopathological features of Huntington's disease. In the present study, serial 1H-NMR spectroscopy (1H-MRS) assessment of striatal and occipital cortex concentrations of N-acetylaspartate, phosphocreatine/creatine, choline, and lactate, were obtained every 2-weeks during the entire course of a chronic 3NP treatment in baboons. A region-selective increase in lactate was detected in the striatum of the 3NP-treated animals, either immediately before or in conjunction with a lesion in the dorsolateral putamen detected by T2-MR imaging. Absolute 1H-MRS quantitation demonstrated a progressive and region-specific decrease in striatal N-acetylaspartate, creatine, and choline, occuring as early as 3 weeks before the first detection of lactate. These results demonstrate that 1H-MRS can be used to monitor early stages of brain metabolic impairment. In addition, given that 3NP-induced SDH inhibition following systemic injection similarly affects all brain regions, the striatal selective decreases in N-acetylaspartate or creatine concentrations are not simply related to the level of mitochondrial impairment but to a preferential vulnerability of the striatum to 3NP-induced toxicity.
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PMID:Serial 1H-NMR spectroscopy study of metabolic impairment in primates chronically treated with the succinate dehydrogenase inhibitor 3-nitropropionic acid. 1044 53

To investigate the mechanisms of neuronal death in neurodegeneration, in vivo localized proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion-weighted MRI (DWI) were used to evaluate temporal changes in rat striata after administration of 3-nitropropionic acid. It was found that N-acetylaspartate (NAA) reduction, with nearly simultaneous evidence of striatal lesions in DWI, was preceded by a significant and progressive increase of acetate. Shortly before the NAA levels decreased to the lowest point, acetate levels peaked and began to gradually decline toward the control levels. These results suggest that acetate increase may arise from fatty acid degradation, inhibition of succinate dehydrogenase and possible NAA hydrolysis. The elevated acetate may provide a source of acetyl group for membrane repair during excitotoxic brain injury. Magn Reson Med 44:29-34, 2000.
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PMID:Temporal changes of cerebral metabolites and striatal lesions in acute 3-nitropropionic acid intoxication in the rat. 1089 18