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ABSTRACT: L-arginine, one of the most metabolically versatile amino acids, can be metabolized to form a number of bioactive molecules. The present study systematically investigated age-related changes in L-arginine and its metabolites in the hippocampus, parahippocampal region, and prefrontal cortex at the tissue (crude homogenates) and synaptoneurosome (a subcellular preparation enriched for synaptic material) levels. As aging leads to reduced water content in the brain, age-related changes in neurochemical levels in tissue homogenates normalized by wet tissue weight and protein level were compared. There were significant differences in L-arginine, L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, and glutamate, but not GABA, in the CA1, CA2/3, and dentate gyrus sub-regions of the hippocampus and the prefrontal, entorhinal, perirhinal, and postrhinal cortices in 24 (aged) and 4 (young) months old rats in a region-specific manner. The overall pattern of age-related changes in amino acids (L-arginine, L-citrulline, L-ornithine, glutamate, and GABA) was largely similar between homogenates and synaptoneurosomes, whereas the pattern for the amines (agmatine, putrescine, spermidine, and spermine) was quite different. Furthermore, the pattern of age-related changes in neurochemical levels in tissue homogenates normalized by wet tissue weight and protein level was very similar for all 9 neurochemicals measured. These findings suggest that there are differential effects of aging on L-arginine metabolism at the tissue and synaptoneurosome levels and that the way of data normalization (tissue weight vs. protein level) has no or very minor effects on 9 neurochemicals measured.
Neuroscience 02/2012; 209:21-31. · 3.38 Impact Factor
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ABSTRACT: L-arginine is metabolised by nitric oxide synthase (NOS) and arginase to form L-citrulline and nitric oxide, and L-ornithine and urea, respectively. The present study investigated NOS and arginase activities, and the levels of L-arginine, L-citrulline and L-ornithine, as well as glutamate and gamma-aminobutyric acid (GABA), in memory-related brain structures in 4, 12 and 24 months old rats. Significantly increased NOS and arginase activities with age were found across the CA1, CA2/3 and dentate gyrus (DG) sub-regions of the hippocampus and the prefrontal, entorhinal, perirhinal, postrhinal and temporal cortices in a region-specific manner. For L-arginine, there were age-related increases in CA1 and the perirhinal and temporal cortices, and decreases in the entorhinal and postrhinal cortices. L-citrulline levels were decreased with age in the prefrontal, postrhinal and temporal cortices. There were age-related decreases in L-citrulline/L-arginine molar ratio in CA1 and CA2/3 and the prefrontal and temporal cortices, but an increase in the entorhinal cortex (EC). Increased L-ornithine levels and L-ornithine/L-arginine molar ratios with age were found in most of the brain regions examined. Glutamate levels were significantly decreased with age in the prefrontal, entorhinal, perirhinal and temporal cortices, whereas GABA level was largely unchanged except for age-related increase in CA1. There were significantly decreased glutamate/GABA molar ratios with age in six brain regions. Correlational analyses revealed no inverse relationship between NOS and arginase activities, and no positive correlations between the activities of the two enzymes and the tissue concentrations of their products. Interestingly, there were significant positive correlations between glutamate and GABA, and L-arginine and its metabolites in many brain regions. These results demonstrate that the aging process has dramatic effects on the NOS and arginase metabolic pathways of L-arginine and the glutamatergic neurotransmitter system. Since L-arginine metabolism is complex, there is a need to determine its metabolomic profile in vivo in the future.
Neuroscience 09/2009; 164(2):611-28. · 3.38 Impact Factor
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ABSTRACT: Polyamines putrescine, spermidine and spermine are positively charged aliphatic amines and have important roles in maintaining normal cellular function, regulating neurotransmitter receptors and modulating learning and memory. Recent evidence suggests a role of putrescine in hippocampal neurogenesis, that is significantly impaired during aging. The present study measured the polyamine levels in memory-related brain structures in 24- (aged), 12- (middle-aged) and 4- (young) month-old rats using liquid chromatography/mass spectrometry and high performance liquid chromatography. In the hippocampus, the putrescine levels were significantly decreased in the CA1 and dentate gyrus, and increased in the CA2/3 with age. Significant age-related increases in the spermidine levels were found in the CA1 and CA2/3. There was no difference between groups in spermine in any sub-regions examined. In the parahippocampal region, increased putrescine level with age was observed in the entorhinal cortex, and age did not alter the spermidine levels. The spermine level was significantly decreased in the perirhinal cortex and increased in the postrhinal cortex with age. In the prefrontal cortex, there was age-related decrease in putrescine, and the spermidine and spermine levels were significantly increased with age. This study, for the first time, demonstrates age-related region-specific changes in polyamines in memory-associated structures, suggesting that polyamine system dysfunction may potentially contribute to aged-related impairments in hippocampal neurogenesis and learning and memory.
Neuroscience 07/2008; 155(3):789-96. · 3.38 Impact Factor
