Tocopherol-associated protein is a ligand-dependent transcriptional activator.

Vitamin E is a term that encompasses a group of potent, lipid-soluble, chain-breaking antioxidants. Structural analysis reveals that molecules having vitamin E activity include four isomers (alpha, beta, gamma, and delta) of both tocopherols and tocotrienols. Alpha-tocopherol has been shown to have the highest biological vitamin E activity in mammalian tissues based on fetal resorption assays, and it reverses vitamin E deficiency symptoms. Although the molecular functions fulfilled specifically by alpha-tocopherol have yet to be fully described, it is unlikely that they are limited to general antioxidant functions. Here we show the functional characterization of alpha-tocopherol associated protein, TAP, which displays significant sequence similarity to the alpha-tocopherol transfer protein. Ligand competition analysis showed that recombinant TAP binds to alpha-tocopherol but not to other isomers of tocopherols. Using GFP fusion protein expression system, we observed that TAP translocates from cytosol to nuclei in alpha-tocopherol-dependent fashion. Transient transfection experiment showed that TAP activates transcription of the reporter gene in alpha-tocopherol-dependent manner. These results suggest that the biological function of alpha-tocopherol is not only as an antioxidant but also as a transcriptional regulator of gene expression via association with a transcription factor TAP.

A mainstay of functional food science in Japan--history, present status, and future outlook.

The development of food science in the near future probably depends on the advance in functional food science, the concept of which was proposed first in Japan nearly 15 years ago. The new science has been internationally distributed and accepted as conceptually being beyond nutrition. In Japan, however, it traced a unique path of progress in the form of a product-driven rather than concept-driven science. Actually, a number of substances and products with potential for disease risk reduction rather than simply for health maintenance have been investigated for their body-modulating functions. Some of them have been applied in practice to the industrialization of functional foods in terms of "foods for specified health uses" legally defined by new legislation. A variety of sophisticated methods have been introduced as well, including the so-called "XYZ" evaluation system, database construction for assessment of the function, and even the DNA microarray technique. The Ministry of Agriculture, Forestry, and Fisheries (MAFF) and the Ministry of Health and Welfare (MHW) also commenced their scientific as well as political activity, with its spread to industries which almost simultaneously began to vigorously investigate functional food products for enlargement of the food market. With all of this as a background, the Japan Liaison of the International Union of Food Science and Technology (IUFoST) hold a function food science symposium on behalf of related scientific bodies including the Japan Section of the International Life Science Institute (ILSI). This paper is an overview compiled from 12 presentations made in the symposium, with the aim of internationally publicizing the activity of functional food science in Japan.

Ginkgo biloba extract attenuates the development of hypertension in deoxycorticosterone acetate-salt hypertensive rats.

1. We examined the effects of Ginkgo biloba extract (GBE) on the development of hypertension, platelet activation and renal dysfunction in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Both DOCA-salt hypertensive rats and normotensive rats were fed a 2% GBE diet for 20 days. Blood pressure (BP) was measured by two methods, namely by the tail-cuff and telemetry methods. 2. Development of hypertension was attenuated in rats fed a 2% GBE diet. In addition, an increase in heart weight, an indicator of sustained high BP, was inhibited significantly by feeding of the GBE diet. 3. Decreases in 5-hydroxytryptamine content in platelets, a marker of platelet activation in vivo associated with hypertension, were also prevented by feeding of the GBE diet. Ginkgo biloba extract itself did not inhibit ADP- and collagen-induced platelet aggregation examined in vitro. Feeding of the GBE diet tended to inhibit increases in plasma urea nitrogen due to hypertension. 4. The telemetry study demonstrated that BP and heart rate (HR) showed a clear circadian rhythm and the antihypertensive effect of GBE was prominent in the daytime, a resting period for rats. This anti-hypertensive effect of GBE was not detected in normotensive rats. In contrast, the inhibitory effect of GBE on HR was independent of time and was observed in both normotensive and hypertensive rats. 5. These results indicate that GBE has an anti-hypertensive and bradycardiac action, which are time dependent and independent, respectively. Thus, it appears that the chronopharmacological action of GBE may be ascribed not to pharmacokinetic factors, but rather to a circadian susceptibility rhythm to GBE in DOCA-salt hypertensive rats.

Increases in 4-hydroxynonenal and hexanal in bone marrow of rats subjected to total body X-ray irradiation: association with antioxidant vitamins.

Radiation-induced lipid peroxidation and its association with antioxidant vitamins in the bone marrow (BM), of rats subjected to total body irradiation (TBI) of X-rays at a dose of 3 Gy was investigated. The concentration of vitamin C in the BM decreased at 4 h, and reached about 2% of the control level at 24 h after irradiation. The concentration of vitamin E in the BM also decreased to 43% at 24 h. Corresponding to the decrease in vitamin E concentration, the concentration of 4-hydroxynonenal (HNE) in the BM increased 2.5-fold at 24 h. Similarly, increases in the concentrations of hexanal and thiobarbituric acid-reactive substances (TBA-RS) were detected in the BM. In the plasma, these parameters of lipid peroxidation were unchanged up to 48 h, but were increased at 96 h after irradiation. Four days of vitamin E administration to rats (p.o. 460 mg/kg body weight) prior to the 3 Gy X-irradiation increased the vitamin E concentration in the BM to 1.3-fold the control level, but did not attenuate the increases in HNE and hexanal in the BM. The slight accumulation of vitamin E in the BM as a result of the vitamin E treatment may be partly related to this lack of vitamin E effect.

Calcium absorption from the ingestion of coral-derived calcium by humans.

Recent dietary life involves frequent opportunities for the ingestion of purified, processed food products and preserved foods, and it has been pointed out that the current dietary mineral intake strongly tends toward nutritional imbalance. The Ryukyu Islands yield coral which contains calcium and magnesium in a content ratio of about 2 to 1, with their approximate contents of 20 and 10%, respectively. In this report, the calcium absorption from the ingestion of crackers into which the coral powder was incorporated (coral-added crackers) and that from ingestion of calcium carbonate-added crackers was comparatively assessed. Twelve healthy adult volunteers (6 men and 6 women) ingested coral-added crackers (calcium content: 525 mg) and calcium carbonate-added crackers (ditto) once each alternately on a cross-over design with a wash-out period of 3 d between the regimens. The study also included controls receiving neither cracker. The degree of intestinal absorption of calcium from coral-added crackers and that from calcium carbonate-added crackers was evaluated in terms of increment in urinary calcium excretion per dL of glomerular filtrate (GF) (difference between coral calcium and calcium carbonate) and increase in urinary calcium excretion per milligram creatinine (difference from control value). The increment in urinary calcium excretion per dL of GF during the latter half of the observation period after the ingestion of coral-added crackers was significantly greater than that during the latter half of the observation period after ingestion of calcium carbonate-added crackers (p = 0.039, paired t-test). A significant difference (from control value) in the increase of urinary calcium excretion per milligram creatinine was also observed (p = 0.0008). The present data, though from a relatively few study subjects, suggest that the calcium of coral origin is better absorbed from the intestine than calcium of calcium carbonate origin on the average.

Effect of dietary magnesium level on nephrocalcinosis and growth in rats.

We studied the extent of kidney calcification by varying dietary levels of Mg, based on pathological examinations and calcium (Ca) and magnesium (Mg) balance tests. AIN-76 diets containing varying levels of Mg--0.3 (-M), 1.3 (1/20M), 2.4 (1/10M), 9.2 (1/5M), 19 (control), 38 (2M), 102 (5M), and 187 (10M) mmol/kg diet--were fed to 3-week-old male Fischer-344 rats for 14d. Although the magnitude of abnormality was highest in kidney of rats fed the -M diet, the damage was normalized as the dietary level of Mg increased, with increasing serum Mg concentration and urinary excretion of Mg. We found almost no deposition of Ca in rats fed the 10M diet. The mechanism by which the high dietary Mg induces these effects most likely involves a competition between Mg and Ca for reabsorption in proximal and/or distal tubules, since these diets increased the urinary excretion of Ca. However, these high Mg diets decreased food intake and body weight gain compared with the control diet, although these indices were not decreased in rats fed the 2M diet. The results suggest that a dietary magnesium level approximately twice the normal level effectively reduces kidney calcification while maintaining normal growth in rats.

Bioavailability of magnesium contained in roasted and ground soybean (kinako) as evaluated by serum and bone magnesium contents, kidney calcification, and magnesium absorption.

The bioavailability of roasted and ground soybean (kinako) magnesium (Mg) in Fischer 344 strain male rats with respect to serum Mg level, bone Mg contents, kidney calcification, and Mg absorption was evaluated. Four-week-old male rats were divided into four groups of six rats each. The four groups were the control (20SC), Mg-deficient diet (1/3 Mg20SC), 20SCK diet, and 20SCDK diet. The 20SCK and 20SCDK diets were prepared to contain amounts of Mg equal to that in the 20SC diet with kinako or defatted kinako as the Mg source, respectively. After a 4-week experimental period, rats were decapitated and blood serum, right femur, and right kidney were collected, and Mg, calcium (Ca), and phosphorus (P) concentration in those tissues were determined. The Mg balance was also investigated. The serum Mg concentration in the 1/3 Mg20SC group was half the level in the 20SC group, and the serum Ca concentration was higher than in the 20SC group, indicating apparent hypercalcemia. Serum Mg and Ca concentrations in the 20SCK and 20SCDK groups did not significantly differ from those in the 20SC group. Femur Mg concentration in the 1/3 Mg20SC group was lower than in the 20SC group. Femur Mg concentrations in the 20SCK and 20SCDK groups were lower than in the 20SC group, but significantly higher than in the 1/3 Mg20SC group. The kidney Ca concentrations in the 20SCK and 20SCDK groups were significantly higher than those in the 20SC and 1/3 Mg20SC groups, and there was also kidney calcification. These results indicated that kinako and defatted kinako Mg were used effectively as a serum and femur Mg source, but that kinako and defatted kinako carry a risk of kidney calcification when used as the only Mg source.

Influence of one bout of intensive running on lymphocyte micronucleus frequencies in endurance-trained and untrained men.

Exercise induced chromosomal damage was evaluated in trained and untrained subjects, who performed treadmill running at 85% of maximal oxygen uptake for 30 min. The subjects had their peripheral blood taken before, immediately after and 30 min after the running test for the analysis of lymphocyte chromosomal damage that was evaluated by micronucleus assay. The blood samples were also subjected to X-ray irradiation in vitro to examine the modification of exercise induced chromosomal damage by a secondarily induced oxidative stress. Spontaneous chromosomal damage in lymphocytes did not significantly increase at least until 30 min after the running both in the trained and untrained subjects. However, the X-ray-induced chromosomal damage was significantly enhanced at 30 min after the running in the untrained group, but not in the trained group. The ratio of X-ray-induced/spontaneous chromosomal damage also tended to increase after the running only in the untrained group. These preliminary results suggest that intensive exercise induced very slight chromosomal damage only in the untrained group, which could be intensified by the secondarily induced oxidative stress.

Feeding mice palm carotene prevents DNA damage in bone marrow and reduction of peripheral leukocyte counts, and enhances survival following X-ray irradiation.

This study examined the effects of palm carotene feeding on DNA damage of bone marrow, recovery of peripheral leukocyte counts, and the survival of mice that received whole-body X-ray irradiation. The palm carotene was composed of alpha- and beta-carotene in a ratio of 1:3. Mice were fed either a basal diet or a carotene diet (50 mg carotene/100 g diet) for 2 weeks, then irradiated. The carotene diet was prepared by the dietary protocol that markedly enhanced the accumulation of carotene in tissues (J. Nutr. 125, 3081, 1995). DNA damage in bone marrow was evaluated by micronucleus assay using peripheral blood. When mice received X-ray (1.5 Gy), marked DNA damage in bone marrow and reduction of peripheral leukocyte count were observed. These changes were significantly attenuated in mice fed the carotene diet. In addition, X-ray (6.5 Gy)-induced survival of mice fed the carotene diet was higher than those fed the basal diet. In mice fed the carotene diet, alpha- and beta-carotene were detected in bone marrow and liver, and concentration of vitamin A in liver was about four times higher compared with that in mice fed the basal diet. These findings suggest that feeding mice palm carotene prevents radiation-induced damages by way of its antioxidant activity and/or vitamin A activity.

Lack of influence of a long-term high or low vitamin E diet on the oxidative DNA damage in the bone marrow of mice.

To investigate the influence of dietary vitamin E (VE) on DNA damage in bone marrow, we fed mice either a low VE diet (-VE), a basal VE diet (+30 mg VE/kg) or a high VE diet (+1000 mg VE/kg) for 50 weeks. DNA damage was evaluated by two cytogenetic methods: micronucleus (MN) assay using peripheral blood, and examination of sister chromatid exchanges (SCE) in bone marrow cells. The MN assay was performed periodically from 6 to 50 weeks, and showed that the incidence of reticulocytes containing MNs did not increase in the low VE diet group, and did not decrease in the high VE diet group. SCE assay done at 50 weeks also showed no difference among the VE diet groups. VE in bone marrow was markedly lower in the low VE diet group and higher in the high VE diet group compared to that in the basal VE diet group at 6 weeks. The VE at 50 weeks was not markedly different from that at 6 weeks. Corresponding to the changes in the VE, lipid peroxide in bone marrow was higher in the low VE diet group, but was not lower in the high VE diet group. Glutathione and vitamin C in the bone marrow, which were about 100-1000 times higher than that of VE, were not different among the groups.

Differences in the influence of AIN-purified and non-purified diets on the development of hypertension in SHR and DOCA-salt hypertensive rats.

The influence of non-purified and AIN purified diets on the development of hypertension was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive rats and SHRs. For DOCA-salt hypertensive rats, the development of hypertension was slower in rats fed the AIN 76-purified diet than in those fed the non-purified diet throughout the experimental period of about five weeks. In an experiment using spontaneously hypertensive rats (SHRs), 4-week-old rats were fed either a non-purified diet, a AIN76-purified diet or a AIN93G-purified diet for about nine weeks. In the first 1-2 weeks, the blood pressure was lower in the SHRs fed the AIN93G-purified diet than in those fed the non-purified diet. However, no significant difference in blood pressure was observed within the SHR group thereafter.

Simultaneous dietary supplementation of sodium cholate and beta-carotene markedly enhances accumulation of beta-carotene in mice.

This study evaluated whether simultaneous supplementation of sodium cholate and beta-carotene to a diet enhanced the accumulation of beta-carotene in mice. For 2 wk, male ICR mice were fed either a basal diet or a diet containing Dunaliella-bardawil beta-carotene 50 mg/100g that was or was not supplemented with sodium cholate (0.25 g/100 g). The concentrations of beta-carotene in liver and plasma were approximately 5 and 10 times higher, respectively. In the mice fed the beta-carotene diet with sodium cholate than in those fed the beta-carotene diet without sodium cholate. Beta-carotene was not detectable in the liver or plasma of mice fed either basal diet. The concentrations of vitamin E in the plasma and liver of mice fed either beta-carotene diet or the basal diet with sodium cholate were significantly lower than in those fed the basal diet. In a second study, mice were fed a diet containing 50 mg/100 g synthetic beta-carotene supplemented with various concentrations of sodium cholate (0, 0.05, 0.1, 0.25, 0.5 g/100 g) for 2 wk. The concentrations of beta-carotene and vitamin E in plasma, liver and bone marrow cells were higher in mice fed the beta-carotene diet supplemented with 0.05 g/100 g of sodium cholate than in those fed the unsupplemented diet. These findings show that simultaneous supplementation of sodium cholate and beta-carotene to a diet markedly enhances the accumulation of beta-carotene. This dietary protocol may be useful to introduce a high amount of beta-carotene in the tissue of mice in a short period of time.

Whole body X-ray irradiation to mice decreases ascorbic acid concentration in bone marrow: comparison between ascorbic acid and vitamin E.

The change in the ascorbic acid concentration in the bone marrow after whole body X-ray irradiation was compared with that in the vitamin E concentration. The ascorbic acid concentration in the bone marrow significantly decreased by 30% 1 h after exposure to 3 Gy of X-rays, whereas the vitamin E concentration in the bone marrow was significantly decreased 5 h after exposure, when the level of ascorbic acid was less than 10% of that in the control. At 24 h after exposure, the ascorbic acid concentration in the bone marrow was significantly decreased by 80% after exposure to 0.5 Gy, whereas the vitamin E concentration was significantly decreased after exposure to 1 Gy or more. In the bone marrow, the decrease in the ascorbic acid concentration was accompanied by a marked increase in the concentration of dehydroascorbic acid, an oxidized form of ascorbic acid. X-ray irradiation did not decrease either the ascorbic acid or vitamin E concentration in the serum or intestine. These findings suggest that the bone marrow is more highly susceptible to oxidative damage by radiation and that ascorbic acid plays an important defense role against it. On Day 8 after irradiation, the decreases in the vitamin E and ascorbic acid concentrations in the bone marrow showed recovery after exposure to 3 Gy, but not after the exposure to 6 Gy.

Feeding of palm oil carotene to mice did not modify X-ray-induced chromosomal damage in bone marrow cells.

The influence of palm oil carotene treatment on X-ray-induced chromosomal damage in bone marrow cells of mice was studied. Palm oil carotene contains alpha- and beta-carotene in a ratio of 1:3. Mice were fed either a basal diet or carotene diet containing 50 mg of palm oil carotene/100 g for 15 days. On day 13, mice to be X-ray-irradiated received 0.5 Gy of X-ray to their whole bodies, and the chromosomal damage in bone marrow cells was evaluated in terms of the percentages of micronucleated reticulocytes in their peripheral blood on day 15. The chromosomal damage in the X-ray irradiated mice was 10 times higher than that in the unirradiated mice. The feeding of the carotene diet did not prevent the X-ray-induced chromosomal damage. In the bone marrow cells of mice fed the carotene diet, alpha- and beta-carotene were detected, but the concentration of the carotenes was less than one-hundredth of that of vitamin E. In addition, the feeding of carotene diet markedly reduced the concentration of vitamin E in bone marrow cells and serum. The X-ray irradiation reduced the concentration of vitamin C in the bone marrow cells, but did not reduce that of vitamin E or carotene in the cells.

Bioavailability of magnesium contained in purple laver (Asakusa-Nori) by rats with scarce magnesium, being evaluated from serum magnesium, kidney calcification, and bone magnesium contents.

An experiment was designed to evaluate the bioavailability of purple laver (Asakusa-Nori, Porphyra tenera Kjellman) magnesium (Mg) in Mg-scarcity Fischer 344 male rats from serum Mg level, kidney calcification and bone Mg contents. Male rats of 4 weeks of age were divided into four groups of six rats. The four groups were control (20SC), Mg-restricted (-Mg20SC), -Mg20SC plus purple laver (-Mg20SCP), and 20SC plus purple laver (20SCP) group respectively. To -Mg20SC, 1/10 Mg of the 20SC diet was added. -Mg20SCP diet purple laver as a Mg source. 20SCP diet was designed to contain double amount of Mg. After a 3-week experimental period, rats were decapitated. Blood serum, right kidney, and right femur were collected and Mg, calcium (Ca), phosphorus (P) were determined. Serum Mg concentration of the -Mg20SC was 1/3 of the 20SC, indicating apparent hypomagnesemia. Serum P also showed lowered concentration. On the other hand, the serum Ca indicated higher value than the other groups, indicating hypercalcemia. Addition of purple laver to -Mg20SC diet resulted in a normal serum Mg, Ca, and P level. The Mg-scarcity (-Mg20SC) rats accumulated much amount of kidney Ca. Whereas, there was no significant difference in kidney Ca between control (20SC) group and purple laver-supplemented (-Mg20SCP) rat group. The -Mg20SC rats showed lowered ash content and reduced Mg and P concentrations in the femur. Purple laver supplementation increased the ash, Mg, and P. All of the results indicated that the purple laver Mg was used as a Mg source.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of protein intake on mineral (calcium, magnesium, and phosphorus) balance in Japanese males.

A 26-day balance study was conducted to examine the effect of a high protein diet on calcium, magnesium, and phosphorus utilization in six healthy males (age 20-22 years, body weight 54.0-64.4 kg, body height 165-173 cm). In addition, the effect of physical exercise on calcium, magnesium, and phosphorus balance was also examined. After a 2-day stabilization period, two levels of protein--control (1.0 g/kg of body weight) and high (2.0 g/kg of body weight) protein--diets were given for three 4-day periods at each protein level. During the last 4-day period of each protein level, subjects exercised on a bicycle ergometer for two 1-h periods daily at a load of 1.5 kp., 50 cyc./min. The high protein diet increased urinary calcium and caused a significant negative calcium balance. Magnesium balance tended to be negative in the control diet. There were no significant changes in urinary calcium, magnesium, and phosphorus and also in the calcium, magnesium, and phosphorus balance during physical exercise.

The sympathetic nervous system response to stress in chronic vitamin E-deficient rats.

This study was undertaken to examine whether some stressful conditions affected urinary output of catecholamine of 3- and 18-month-old vitamin E-deficient rats and control rats. Basal levels of urinary norepinephrine (NE) and epinephrine (E) excretion of aged vitamin E-deficient rats was 2- to 3-fold higher than those of control rats. In both groups of young rats, cold exposure, administration of insulin, and immobilization stress provoked a marked increase in urinary output of NE, E, NE and E, respectively. However, the urinary catecholamine responses to these stresses were markedly diminished in aged rats. No significant changes were observed in excretion of catecholamine during these stresses in aged rats receiving vitamin E-deficient diet. Therefore, these results suggested that the responses of sympathetic nervous activity to these stresses were significantly lowered in the chronic vitamin E-deficient rats compared to control rats.

Effect of diet on sympathetic nervous system activity in chronic vitamin E-deficient rats.

This study was undertaken to examine the responsiveness of the sympathetic nervous system of chronic vitamin E-deficient rats to dietary changes. Rats receiving a vitamin E-deficient diet exhibited about 95% hemolysis after 4 weeks on the vitamin E-deficient diet and this value was maintained up to 18 months. alpha-Tocopherol in serum was not detectable in rats receiving the vitamin E-deficient diet for 18 months. Lipid peroxide concentration in serum of rats receiving the vitamin E-deficient diet for 18 months was 10-fold higher than that of control rats. Basal levels of urinary norepinephrine (NE) and epinephrine (E) excretion in chronic vitamin E-deficient rats was 2- to 3-fold higher than those of control rats. In control rats, urinary NE excretion declined during fasting and this decline was reversed upon refeeding. Urinary excretion of NE in control rats increased upon glucose feeding. However, in chronic vitamin E-deficient rats, no change was observed upon fasting and glucose feeding in either urinary NE or E excretion. These results suggest that the increase in basal levels of urinary NE excretion in chronic vitamin E-deficient rats was not influenced by dietary manipulation.

Age-related changes in sympathetic nervous activity of rats receiving vitamin E-deficient diet.

To study the relationship between age-related stimulation of sympathetic nervous activity and vitamin E, excretion of urinary catecholamine and the contents of organ catecholamine were measured in rats receiving a vitamin E-deficient or control diet for 95 weeks. Rats exhibited about 95% hemolysis after 4 weeks on the vitamin E-deficient diet and this value remained the same for 95 weeks. alpha-Tocopherol in plasma was not detectable in the deficient diet-fed rats, and lipid peroxide concentrations in the plasma, liver and adrenal glands of rats receiving the vitamin E-deficient diet for 95 weeks were 3- to 30-fold higher than those of control rats. Urinary excretion of catecholamine (norepinephrine (NE), epinephrine (E) and dopamine (DA] increased with age. Excretion of NE in 24-h urine of rats receiving the vitamin E-deficient diet for 50 and 95 weeks was 2- to 3-fold higher than that of control rats, although no significant difference was observed at week 12. Contents of NE and E in the adrenal glands and of NE in the heart from the deficient rats were significantly lower than those of control rats at week 95. These results suggest that sympathetic nervous activity is enhanced in aged rats and that the sympathetic nervous activity in vitamin E-deficient rats is greater than in control rats.

Effect of 3-acetylpyridine on the development of rat brain.

3-Acetylpyridine, an antagonistic agent of nicotinic acid, was given to suckling rats from 6 days of age. Rats were killed at 6, 9, 12, 15, 18, 21, 24, 27 and 30 days of age respectively, and their brains were analyzed for several biochemical parameters of brain growth and myelination for comparison with those of pair-fed and ad libitum control rats. Results of DNA, RNA and protein content measurements in the brain of rats which had received 3-acetylpyridine and of pair-fed control suggested a retardation of about one week in brain growth and development compared to ad libitum control with most striking differences noted at 12 days of age. At 30 days of age, rats which had received 3-acetylpyridine showed lower values in yield of myelin, content of cerebroside and specific activity of 2', 3'-cyclic nucleotide-3-phosphohydrolase, when compared with pair-fed and ad libitum controls. These results indicate that undernourishment due to restricted food intake during brain growth-spurt results in retardation of brain development to some extent. They also suggest that nicotinic acid plays an important role in myelination associated with synthesis of cerebroside which contains high levels of long-chain fatty acid.