Effect of Dietary γ-Aminobutyric Acid on the Brain Protein Synthesis Rate in Hypophysectomized Aged Rats

Abstract

SummaryThe 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 ␥ -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 ϩ 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. Key Words ␥ -aminobutyric acid, growth hormone, protein synthesis, brain, ratsThe metabolic response to dietary proteins, age and hormonal factors includes marked changes in protein synthesis, especially in the liver, muscles and intestines ( 1-5 ). Protein synthesis in the brain is also sensitive to the alteration of dietary amino acid composition in young rats ( 6 , 7 ).Many investigators have reported that protein synthesis declines in specific tissues (e.g., liver or muscle) and in the whole body throughout development in mammals after weaning ( 8-10 ). We demonstrated that the rate of protein synthesis in the brain decreases with age in rats after weaning ( 11 ). In many investigations, not only age but also growth hormone (GH) deficiency has been shown to affect many functions related to the central nervous system in mammals ( 12 ). GH is well known as the anabolic hormone in protein metabolism. Several investigators have demonstrated that the protein synthesis in visceral organs, skeletal muscle and brains was increased by GH in rats ( 13 , 14 ).␥ -Aminobutyric acid (GABA) is a kind of amino acid widely distributed over the nature, and is an inhibitory transmitter compound in vertebrates ( 15 , 16 ). Recently, GABA was attracted attention as a functional food for improvement in memory and study capability, bloodpressure reduction and relaxation inducement ( 17 , 18 ). In a previous study, we reported that administration of GABA to young and aged rats increased the concentration of plasma GH and the rate of protein synthesis in the brain, and that a positive c...

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“…Investigators have reported that growth hormone was increased after GABA intake (21)(22)(23). Moreover, previous studies have shown that the increase in growth hormone level correlated to protein synthesis rate in the brain (21).…”

Effect of Dietary ^|^gamma;-Aminobutyric Acid on the Nerve Growth Factor and the Choline Acetyltransferase in the Cerebral Cortex and Hippocampus of Ovariectomized Female Rats

“…The GH-binding receptor has been identified in the brains of humans and rats (32). Recently, we (33) reported that dietary GABA increased the rate of brain protein synthesis in sham-operated rats, and did not affect the rate of brain protein synthesis in hypophysectomized rats. Thus, the GABA-induced increase in the concentration of GH may be primarily responsible for changes in the brain protein synthesis (33).…”

“…Recently, we (33) reported that dietary GABA increased the rate of brain protein synthesis in sham-operated rats, and did not affect the rate of brain protein synthesis in hypophysectomized rats. Thus, the GABA-induced increase in the concentration of GH may be primarily responsible for changes in the brain protein synthesis (33). In Experiment 3, a transiently higher plasma concentration of GH was observed after feeding GABA diet; however, the food intake did not differ between the experimental groups (Table 4).…”

Changes in Thyroid Hormone Are Not Involved in Regulating Brain Protein Synthesis in Adults Rats Fed Ornithine

“…However, a positive correlation between the rate of protein synthesis and RNA activity was found in the brain of aged rats when dietary protein and amino acids were manipulated (29,30). Hormonal treatments such as GH and thyroid hormone also elevated the rate of protein synthesis and RNA activity in the brain (12,17).…”