C. V. Ramakrishnan

Studies on polyphosphoinositides in developing rat brain.

Polyphosphoinositides in rat brain exist in two forms: the metabolically active form that is readily attacked by the polyphosphoinositide phosphohydrolases, and the inert form that is attacked by the enzymes at a slower rate. The two pools continue to increase even during the postweaning period, suggesting a role in glial as well as myelin development apart from their role in neurons.

Effects of Nutritional Rehabilitation on the Content and Lipid Composition of Brain Gray and White Matter of Neonatally Undernourished Rats

Abstract: Neonatal undernutrition affects the content and lipid concentrations of gray and white matter. Nutritional rehabilitation reverses the deficit observed in gray matter. In the case of white matter the lipid concentration but not the content comes back to normal.

EFFECT OF DIETARY PROTEIN CONTENT ON REGIONAL DISTRIBUTION OF ASCORBIC ACID IN THE RAT BRAIN

IT IS not, perhaps, coincidental that tissues such as liver, kidney and adrenals which have a high concentration of ascorbic acid are also sites of considerable metabolic activity. Although the brain, next to the adrenals, has the highest concentration of ascorbic acid, the metabolic significance of this has not received comment. In the rat, an animal which synthesises ascorbic acid, the tissue concentration of the vitamin has been found to increase in conditions such as drug treatment (LAHIRI and LLOYD, 1962; BURNS, CONNEY, DAYTON, EVANS, MARTIN and TALLER, 1960) and cold exposure (MONIER, BAYERS and WEISS, 1953). The increase would appear to be in the form of ascorbic acid since LAHIRI and LLOYD (1962) observed that corticotrophin increased the ascorbic acid content of liver and kidney but decreased dehydroascorbate plus dioxogulonate in rats. In animals such as the guinea pig and man requiring vitamin C, excretion in the urine is found to increase with drug treatment and decrease with cold exposure. Other conditions such as vitamin deficiencies, X-irradiation and inanition are found to decrease urinary excretion and/or tissue concentration of ascorbic acid in rats, but studies of these changes have mainly been confined to the liver, kidney and adrenals. The ascorbic acid status of the brain has not been generally studied, possibly because it was widely believed until recently that the chemical composition of the brain is not subject to much variation. Previous studies in this laboratory showed that protein deficiency in the rat is associated with changes in several enzymes and substrates concerned with glutamic acid metabolism (RAJALAKSHMI, GOVINDARAJAN and RAMAKRISHNAN, 1965). This condition has also been reported to be associated with a decrease in the urinary excretion of ascorbic acid and its concentration in the liver, kidney and adrenals (YANOVASKAYA, 1952 ; BHAGAWAN, RAO and SHRINIVASAN, 1961 ; CHANDRASEKHARA, RAO and SHRINIVASAN, 1963). Since the high concentration of ascorbic acid in the brain varies under conditions of stress such as cold exposure and drug treatment it was of interest to investigate its response to protein deficiency. In this connexion, it was reported (GRIEG, 1947) that the decreased respiration of the cerebral cortex and increased glycolysis following administration of pentobarbitone are restored to normal levels by addition of ascorbic acid. The intraveinous injection of dehydroascorbic acid in rats produces CNS stimulation similar to that following the injection of adrenaline and is accompanied by a doubling of the concentration of ascorbic acid in the brain tissue; this suggests an important role for the vitamin in brain function.

Effects of different levels of dietary protein on brain glutamate dehydrogenase and decarboxylase in young albino rats.

Abstract— Studies were carried out to identify the minimum levels of protein (casein) needed in the diet in order to prevent or reverse the deficits in brain enzymes previously found with protein deficiency. Groups of weanling albino rats were fed diets containing variable amounts of protein (5, 8, 10, 15 or 20 per cent in experiment I, and 5, 6, 7, 8 or 20 per cent in experiment II) for 5 or 10 weeks. Deficits in brain wt and brain glutamate dehydrogenase and decarboxylase were found to be prevented by a diet containing 8 per cent or more of protein, although for optimum growth 15 per cent protein in the diet was found to be necessary. Groups of rats were fed a 5 or 20% protein diet for 10 weeks after which the 5% protein animals were either continued on the diet for another 10 weeks or changed to one containing 8, 10, 15 or 20% protein. The brain enzyme deficits found with the 5% protein diet were found to be fully reversed by feeding a 10% protein diet during rehabilitation.

EFFECTS OF UNDER NUTRITION AND PROTEIN DEFICIENCY ON GLUTAMATE DEHYDROGENASE AND DECARBOXYLASE IN RAT BRAIN

Abstract— Studies were made on the effects of undernutrition at different ages during the neonatal period and of the comparative effects of postweaning protein and calorie deficiencies in neonatally undernourished or normally reared animals. Neonatal undernutrition resulted in deficits in body wt, brain wt and the activities of brain glutamate dehydrogenase and glutamate decarboxylase. Percentage deficits in brain wt were maximum in the first week of life but those in brain enzymes were greater in the second week. Rehabilitation of neonatally undernourished animals reversed the deficits in brain wt and brain enzymes. Post‐weaning protein deficiency produced similar deficits in brain enzymes in both neonatally undernourished and normally reared animals. With post‐weaning undernutrition, however, these deficits were found only in animals subjected to neonatal undernutrition as well.

EFFECTS OF PRE-WEANING AND POST-WEANING UNDERNUTRITION ON ACETYLCHOLINE LEVELS IN RAT BRAIN

Abstract— Studies were made of the effects of undernutrition during the neonatal period and also protein deficiency and undernutrition during the post‐weaning period on brain acetylcholine. Rats undernourished from birth to 4 weeks so as to result in a body wt deficit of 43 per cent had an associated deficit in brain wt of 14 per cent, but the concentration of acetylcholine in the brain was not affected. In the case of post‐weaning undernutrition, acetylcholine concn was found to be affected in protein deficiency as well as in severe calorie restriction.

EFFECTS OF DIFFERENT SUPPLEMENTS TO LOW PROTEIN AND POOR QUALITY PROTEIN DIETS ON PERFORMANCE AND BRAIN ENZYMES IN THE ALBINO RAT

Groups of albino rats were fed low and high protein diets and the former group was fed with different supplements. The supplements used were niacin, pyridoxine and glutamic acid. A low protein diet was found to decrease the activities of l‐glutamate‐NAD‐oxidoreductase and l‐glutamate‐1‐carboxy‐lyase in the cerebrum; this confirmed the results of previous work in this laboratory. Addition of glutamic acid to a low protein diet was found to reverse the effects of a low protein diet to some extent.

Effect of maternal alcohol consumption on the lipid composition of CNS in the offspring

Abstract: Maternal alcohol consumption at a level that does not affect calorie intake increases cholesterol concentration and content as well as incorporation of labeled glucose into cholesterol in the brain and spinal cord of newborn rat pups. Continued consumption of alcohol during lactation also affects the galactolipid concentration in the brain and spinal cord of pups at 21 days of age, and this increase seems mainly to be due to an increase in content of myelin lipids. Analysis of myelin shows that the concentration of phospholipids also increases in this fraction. The increase in incorporation of labeled glucose into these membrane lipids suggests an increase in the synthesis of these lipids, which prevents fluidization of the membrane by alcohol. That in the brainstem the increase in levels of cholesterol and galactolipids is higher than in other regions and that there is also an increase in content of sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine suggest that the brainstem needs better protection against fluidization.

Effect of Ethanol on Rat Brain Polyphosphoinositides

Abstract: Female rats were allowed to consume ethanol during gestation and lactation, and brain polyphosphoinositides of the 21‐day‐old pups were quantified. Ethanol intake prevented the disappearance of the metabolically labile pools of phosphatidylinositol‐4‐phosphate and phosphatidylinositol‐4,5‐bis‐phosphate, which are rapidly degraded in the control group. In contrast, preweaning undernutrition left the size of these pools virtually unchanged, indicating a differential effect of the two nutritional regimens. Key Words: Polyphosphoinositides—Labile pools—Ethanol—Brain of offspring—Phosphati‐dylinositol ‐ 4 ‐ phosphate—Phosphatidylinositol ‐ 4,5 ‐bis‐phosphate—Ethanol feeding—Undernutrition (preweaning). Shah I. R. et al. Effect of ethanol on rat brain polyphosphoinositides.

Lipid composition of gray and white matter in developing rat brain

The lipid composition of gray and white matter was studied in the developing rat brain. For this purpose, gray and white matter were separated from the brains of rats from different age groups and were used for the estimation of moisture and lipids. The moisture content of both gray and white matter decreased with age, but the decrease was more significant in the latter. The concentration of different lipids in gray matter reached adult values at 4 weeks of age, whereas the lipids in white matter showed a slower increase even after this period. Similarly, the content of gray matter reached adult values much earlier (by 3 weeks) than white matter, which continued to increase throughout the period of study. Myelin represented 40% of the dry weight of whitematter. The non‐myelin portion of white matter had a different lipid composition than gray matter, white matter, or myelin.