Influence of GABA on brain protein synthesis mediated by the mammalian target on the rapamycin pathway.

This study determined the influence of γ-aminobutyric acid (GABA) on brain protein synthesis via the mammalian target of rapamycin (mTOR) pathway. Experiments were carried out on three groups of 6-wk-old male rats with 0%, 0.5%, and 1% GABA. The percentage-phosphorylated S6K1 and growth hormone (GH) concentration was significantly increased by the GABA administration. The insulin level was not significantly changed, while the insulin-like growth factor 1 (IGF-1) level was significantly decreased by the GABA administration.

Effect of dietary γ-aminobutyric acid on the brain protein synthesis rate in hypophysectomized aged rats.

The purpose of this study was to determine whether the regulation of brain protein synthesis was mediated through changes in the plasma concentration of growth hormone (GH) when dietary γ-aminobutyric acid (GABA) treatment was manipulated in hypophysectomized or sham-operated aged rats. Experiments were done on four groups of hypophysectomized and sham-operated (24-wk-old) male rats given 0% or 0.5% GABA added to a 20% casein diet. The concentrations of plasma GH and fractional rates of protein synthesis in the brains increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone in the sham-operated rats. However GABA treatment to the basal diet did not affect the rates of protein synthesis in the hypophysectomized rats. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA·d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was also related to the fractional rate of protein synthesis in these organs. The results suggest that treatment with GABA is likely to increase the concentrations of GH and the rate of brain protein synthesis in sham-operated rats only, not in hypophysectomized rats, and that the GABA-induced increase in the concentration of GH may be primarily responsible for changes in the brain protein synthesis. The RNA activity is at least partly related to the fractional rate of brain protein synthesis.

Effect of the quality of dietary amino acids composition on the urea synthesis in rats.

We have shown that urinary urea excretion increased in rats given a lower quality protein. The purpose of present study was to determine whether the composition of dietary amino acids affects urea synthesis. Experiments were done on three groups of rats given diets containing a 10% gluten amino acid mix diet or 10% casein amino acid mix diet or 10% whole egg protein amino acids mix diet for 10 d. The urinary excretion of urea, the liver concentration of N-acetylglutamate, and the liver concentration of free serine, glutamic acids and alanine were greater in the group given the amino acid mix diet of lower quality. The fractional and absolute rates of protein synthesis in tissues declined with a decrease in quality of dietary amino acids. The hepatic concentration of ornithine and the activities of hepatic urea-cycle enzymes were not related to the urea excretion. These results suggest that the increased concentrations of amino acids and N-acetylglutamate seen in the liver of rats given the amino acid mix diets of lower quality are likely among the factors stimulating urea synthesis. The protein synthesis in tissues is at least partly related to hepatic concentrations of amino acids. The composition of dietary amino acids is likely to be one of the factors regulating urea synthesis when the quality of dietary protein is manipulated.

Genistein regulated serotonergic activity in the hippocampus of ovariectomized rats under forced swimming stress.

The mortality of individuals suffering from depression has been increasing, especially post-menopausal women; therefore, their care and treatment are important to maintain a high quality of life. In the present study, we evaluated the antidepressant-like effects of a major isoflavonoid, genistein (4',5,7-trihydroxyisoflavone), using a behavioral model of depression, the forced swimming test (FST), in ovariectomized rats. Daily administration of genistein to ovariectomized rats at a dosage of 10 mg/kg of body weight/d for 14 d significantly reduced the immobility time during the FST without changing motor dysfunction. On the other hand, a higher dosage, 100 mg/kg/d, did not have any effects on the immobility time compared with the vehicle control. Repeated administration of genistein at 10 mg/kg of body weight did not affect serotonergic activities in the hippocampus compared to the vehicle control in ovariectomized rats. A 5-min FST trial stimulated these activities. On the other hand, repeated pretreatment with genistein protected against changes in activity during the FST trial. These results suggest that daily consumption of genistein 10 mg/kg/d might have antidepressant-like effect on ovariectomized rats by regulating changes in serotonergic metabolism in the hippocampus under stressful conditions.

Effect of quality and quantity of dietary protein on 4E-BP1 and S6K1 phosphorylation of brains in aged rats.

We have shown that the rate of brain protein synthesis in aged rats depended on the quality and quantity of dietary protein consumed. The purpose of this study was to determine whether the quality and quantity of dietary protein affected the phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (S6K1) and regulated the brain protein synthesis. Two experiments were done on three groups of 24-wk-old male rats given diets containing 20% casein, 20% gluten, or 20% gelatin (Experiment 1), and 20% casein, 5% casein or 0% casein (Experiment 2) for 10 d. The phosphorylation of S6K1 in both the cerebral cortex and cerebellum, and the phosphorylation of 4E-BP1 in the cerebral cortex declined with a decrease of quality and quantity of dietary protein. The phosphorylation of 4E-BP1 in the cerebellum did not differ among groups. The results suggest that the ingestion of a higher quality and quantity of dietary protein stimulates the phosphorylation of 4E-BP1 and S6K1 in the brain and increases the brain protein synthesis in the aged rats.

Changes in N-acetylglutamate are involved in regulating urea synthesis in rats given a low gluten diet supplemented with L-lysine, L-methinone and L-threonine.

We have shown that urinary urea excretion decreased in rats fed a low gluten diet supplemented with dietary limiting amino acids. The purpose of present study was to determine whether the addition of dietary limiting amino acids to a low gluten diet affected the synthesis and degradation of N-acetylglutamate and regulated urea synthesis. Experiments were done on two groups of rats, given diets containing 10% gluten or 10% gluten+0.5% L-lysine, 0.2% L-threonine and 0.2% L-methionine for 10 d. The urinary excretion of urea, and the liver concentration of N-acetylglutamate, and the liver activity of N-acetylglutamate synthetase decreased with the addition of dietary L-lysine, L-threonine and L-methionine. N-Acetylglutamate concentration in the liver was closely correlated with the N-acetylglutamate synthetase activity in the liver and excretion of urea. The greater degradation of N-acetylglutamate was observed in the group fed the 10% gluten+L-lysine, L-threonine and L-methionine. The hepatic concentration of glutamate and plasma concentration of arginine were not related to the N-acetylglutamate concentration in the liver. These results suggest that the addition of limiting amino acids to the low gluten diet controls the synthesis and degradation of N-acetylglutamate in the liver and lowers urea synthesis.

Dietary gamma-aminobutyric acid affects the brain protein synthesis rate in ovariectomized female rats.

The purpose of this study was to determine whether gamma-aminobutyric acid (GABA) affects the rate of brain protein synthesis in ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to the 20% casein diet. The concentrations of plasma growth hormone (GH) increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone. In the brain regions, GABA treatment to the basal diet elevated significantly the fractional and absolute rates of protein synthesis. In brain regions, the RNA activity [g protein synthesized/(g RNA x d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis. The results suggest that the administration of GABA to ovariectomized female rats is likely to increase the concentrations of plasma GH and the rate of protein synthesis in the brain, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.

The growth hormone affects the brain protein synthesis rate in hypophysectomized aged rats.

The purpose of this study was to determine whether the growth hormone (GH) affects the rate of brain protein synthesis in hypophysectomized aged rats. Experiments were conducted on three groups of 24-wk-old male rats: group 1 were hypophysectomized to reduce the level of plasma GH, group 2 were hypophysectomized and treated with GH and group 3 were sham-operated controls. The fractional rates of protein synthesis in the brains of hypophysectomized rats with GH were significantly greater than those in hypophysectomized rats without GH. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA.d)] significantly correlated with the fractional rate of protein synthesis (r>0.88, p<0.001). The RNA concentration (mg RNA/ g protein) was also related to the fractional rate of protein synthesis in these organs (r>0.56, p<0.05). The results suggest that the treatment of GH to hypophysectomized aged rats is likely to increase the rate of protein synthesis in the brain, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis.