Low-protein Rats Research Articles

Investigations into the etiology of elevated serum T 3 levels in protein-malnourished rats

Thyroid function studies and the peripheral metabolism of thyroid hormone were examined in rats fed a low protein diet (9% casein) for 4–8 wk. Compared to animals fed a normal protein diet ad libitum, both the low protein rats and a pair-fed control group weighed less at the end of the study. However, serum total T 3 levels were significantly higher only in the protein deficient rats. The elevated serum T 3 was not explainable by enhanced peripheral T 4 to T 3 conversion, as there was no evidence of any change in hepatic or renal 5′-deiodinase activity when homogenates were examined for conversion of T 4 to T 3, reverse T 3 to 3,3′-diiodothyronine, or 3′,5′-diiodothyronine to 3′-monoiodothyronine. Neither was there an effect on hepatic T 3 receptor maximal binding capacity (204 ± 24 versus 168 ± 15 fmol/mg DNA control) or binding affinity (2.07 ± 0.38 versus 2.49 ± 0.24 × 10 −10 M control). In two separate experiments the dialyzable fraction of T 3 was significantly lower in the low protein group while free T 3 concentrations were unchanged or reduced. In contrast, serum total and free T 4 were either normal or reduced and dialyzable T 4 was unaffected by protein deficiency. We conclude that while serum total T 3 is elevated in rats chronically fed a low protein diet, this elevation is not due to enhanced T 4 to T 3 conversion. Rather, the increased T 3 levels can be accounted for by a striking alteration in protein binding to T 3. Moreover, the failure to demonstrate similar changes in serum total and dialyzable T 4 suggests that in the rat, protein deficiency has different effects on binding to the two major thyroid hormones. Dietary induced changes in serum thyroid hormone binding must be kept in mind in nutrition studies in the rat.

Psychobiological impairment in rats following late-onset protein restriction

Mature rats were kept on protein-deficient diets to test the hypothesis that late-onset protein restriction results in deficits and to determine the feasibility of doing nutrition-behavior research with old naive animals. A 3% low-protein (LP) group and a 24% adequate-protein (AP) pair-fed control were used. Body weights and plasma protein concentrations were lower and exploratory behavior and motor coordination were poorer for LP rats. Both groups preferred the 24% protein diet. LP rats habituated slower and failed to overcome an initial black preference on an oddity discrimination learning task. Nutrition-behavioral research with older rats is feasible, and late-onset protein restriction produces psychobiological deficits.

Food and protein intake, glucagon, and distribution of alpha-aminoisobutyrate in the rat.

Distribution of alpha-aminoisobutyric acid (AIB) in the rat was modified by food, dietary protein, and glucagon. In rats last fed 24 h before AIB injection, AIB clearance from plasma and uptake into liver were greater in rats fed a high-protein diet (60% casein) than in rats fed the control diet (18% casein); AIB clearance from plasma and uptake into muscle were lowered by a low-protein diet (6% casein). Feeding rats lowered clearance of AIB from plasma in low- and high-protein groups. Distribution ratios (AIB concentration in tissue water/AIB in plasma) were low in all tissues but liver during the first 7 h after feeding high protein when compared to the control values; ratios were low in muscle, heart, and kidney after feeding low protein. Maximum ratios occurred at different times for different tissues; the time was delayed by the high-protein diet in all tissues but liver. Glucagon increased all ratios in rats fed the control or low-protein diets, with the smallest changes occurring in liver and muscle from low-protein rats.

Low-protein diet increases sexual behaviour and response to electric shock in adult male rats

Adult male rats were maintained for 4 weeks on an 8% protein diet or a 22% protein diet. During the fifth week the two groups were assessed for sexual behavior, flinch and jump thresholds, and noise-elicited startle habituation. Rats on the low protein diet exhibited significantly more mounting with thrusts and were sensitive to lower levels of shock as indicated by flinch threshold differences. Low protein rats did not differ with respect to jump thresholds or startle response habituation. After a rehabilitation diet the differences in sexual behavior were no longer apparent.

Paranodal myelin retraction in protein deficient and normal rats: a morphometric study.

Young rats, submitted to severe protein restriction were studied concerning the width of inter-myelin gaps at the nodes of Ranvier in peripheral nerve fibres. The results gave no proof of increased paranodal myelin retraction in lumbar spinal roots or the sciatic nerves of low-protein rats. Malnourished rats as well as controls showed great interindividual differences as to the presence of nodes with wide inter-myelin gaps.

The effect of pyrithioxine and pyridoxine on individual behavior, social interactions, and learning in rats malnourished in early postnatal life.

Low protein (LP) or low calorie (LC) dietary regimens were applied in early postnatal life(1st-40th day of life) in male rats. After nutritional rehabilitation, open-field behavior in larger more illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), dyadic interactions, and learning ability were investigated in these animals as adults (between the 200th to 300th day of life). LP malnutrition induced an increase of open-field activity with features of sterotypy both in LI and HI situations, an increase number of intersignal reactions during learning procedures without changes in other registered criteria of learning ability (latency, number of correct responses), and an increase of aggressive behavior in pair interaction. LC rats revealed only significant inhibition in LI--open-field activity and a slightly increased number in intersignal reactions during avoidance learning. With the aim of preventing previously described long-term deviations in early malnourished rats, some groups of animals with the above-mentioned early calorie or protein deficits were treated with pyrithioxine (Encephabol Merck) or pyridoxine in 10 doses of 40 mg/kg i.p. administered in the period when nutritional rehabilitation was carried out (between the 40th--50th day of life). The treatment with pyrithioxine reduced significantly behavioral disturbances in adult LP rats except the increase of intersignal reactions which was even potentiated. Pyridoxine was less effective but normalized the increase number of intersignal reactions both in LP and LC rats. The effect of pyridoxine of adult LC rats was interesting. There was significant improvement in all registered parameters of avoidance learning and a significant increase of sexual acts was recorded.

Development of malnutrition in rats

Male weanling rats were fed either a low protein diet of 0.5% casein, supplemented with methionine, a control diet of 21% casein fed ad libitum, or the 21% casein diet pair-fed to the low protein group for 5 weeks. On the 5th week of the experiment, five animals from the low protein group were rehabilitated onto the 21% casein diet and were continued with the control and pair-fed groups for another 7 weeks. During the first 4 weeks of the experiment, the low protein animals lost 20% of their initial body weight. At the 5th week, two of the four animals killed and three of the five animals rehabilitated showed edema. Body weights of the low protein animals rehabilitated to the 21 % casein diet were still lower than those of the pair-fed and control animals by the 12th week of the experiment. The malnourished rats also exhibited an abnormal accumulation of liver glycogen, which was evident by the 2nd week, and a disturbed electrophoretic pattern of the serum proteins. Transferrin bands were decreased by the 2nd week and remained about the same throughout the rest of the experiment. The prealbumin band was essentially gone by the 2nd week and the albumin was unaffected until the end of the 3rd week, but clearly reduced by the 5th week. The ratios of total concentration of serum free glycine, serine, glutamic acid, glutamine and taurine to leucine, isoleucine, valine and methionine and the ratios of serum free phenylalanine to tyrosine were elevated in low protein rats in agreement with the behavior of these ratios in human kwashiorkor patients.

Early nutrition and the activity and feeding of rats in an artificial environment.

AbstractMale hooded rats were divided into 3 equal groups: (1) controls were given a complete diet ad libitum at all times; (2) for 8 weeks from the age of 28 days, undernourished (UN) rats received the complete diet in restricted amounts; (3) low protein (LP) rats received a low‐protein, high‐carbohydrate diet for the same period. From 12 weeks all rats were given the complete diet ad libitum, until tested at 35 weeks. Each rat was then put alone, for 12 days, in a residential “plus‐maze” with a central nest box and 4 arms radiating from it; food was supplied at the end of one arm, water in the nest box. On Days 4 to 9 each rat had access to the arms for only 1 hr daily. Entries into the arms, and duration of stay, were recorded automatically. All arms were regularly visited by rats of all classes, even when access was only for 1 hr. Visits per day to the 3 nonfood arms combined were usually higher than visits to the food arm, but duration of stay in the food arm was higher than the total duration in the other 3 arms. LP rats made most visits to the arms and were especially active after the 6 days of restriction; but they were less adaptable than the control and UN rats in adjusting food intake during the period of restricted access. In contrast, the UN rats spent most time in the arms.

Postnatal Nutritional Deprivations as Determinants of Adult Rat Behavior toward Food, Its Consumption and Utilization

During the first 7 weeks of life, rats were subjected either to restriction of the quantity of diet of optimal composition or to protein-deficiency malnutrition to learn more about the animals' behavior toward food several months following complete nutritional rehabilitation. The day following parturition female rats were fed a low protein diet (12% casein) for the duration of the nursing period (3 weeks). This resulted in a decreased milk supply and a consequent retardation in the growth of the pups. At weaning, some of the restricted pups were fed for 4 weeks a severely protein-deficient diet (5% casein) which prevented any weight gain during this period (designated low protein). Others were given a diet of optimal composition but in restricted amount so they did not grow during the 4-week experimental period (designated restricted). All animals were then given the normal control diet ad libitum. When adult weight had been reached (6 months of age), the previously low protein and restricted rats were smaller than the controls. Expressed on the basis of body weight0.75, food intake was significantly greater in the previously low protein rats. It is believed this may be accounted for by altered body composition, with a larger percentage of metabolically active tissue in the previously low protein rats. When food spillage was measured in rats fed ad libitum, there was no difference between controls and previously restricted or low protein rats. However, when food availability was limited to 1 hour each day, there was a threefold increase in food spillage in previously low protein, male rats and a significant but much smaller increase in previously restricted, male rats as compared with controls. No difference in food consumption or food spillage was observed in female rats. The food spillage of previously malnourished rats is believed to be one of several manifestations of elevated excitement under stress that have been noted in other studies with adult animals that were severely malnourished in early life. The present studies also confirm and extend previous observations from our laboratories which conclusively show that postnatal nutritional stunting of adult body size is not necessarily correlated with behavioral development. Behavioral abnormalities in the adult that are due to postnatal nutritional deprivations, however, always appear to be accompanied by a stunting of body size. Nitrogen balance studies with both casein and wheat gluten showed no effect of early postnatal malnutrition on nitrogen retention in the adult.

The effect on growth and behaviour of rehabilitating first and second generation low protein rats

Summary o 1. Two experiments are described in which rats fed on a low protein diet were rehabilitated on a laboratory diet containing a higher percentage of protein. In one experiment first generation low protein rats were rehabilitated at weaning and tested on the Hebb-Williams test of animal intelligence and Hall's open field test of emotionality. In the second experiment a second generation of low protein rats were fed the rehabilitation diet from weaning, and their offspring tested by means of a number of developmental tests and the Hebb-Williams test of intelligence. 2. The retardation in the growth and development became more marked as successive generations of rats were reared on the low protein diet. 3. Feeding first generation low protein rats the rehabilitation diet from weaning facilitated their growth, but when mature their problem solving ability remained below that of normal rats. 4. Feeding the second generation low protein rats the rehabilitation diet from weaning and retaining both them and their offspring on the rehabilitation diet did not their offspring on the effects of the low protein diet. The offspring were retarded in growth, development and intelligence. 5. It is concluded that a low protein diet fed to one generation of rats affects the growth and development of the next generation; this seems to be due, at least in part, to a deficiency in the nutrients received from the mother during the foetal period. In rehabilitating low protein rats, more than one generation may have to be fed on a high plane of nutrition before all the effects of the low protein diet are overcome.

Quantum-biological analysis of the relation of urea and its related compounds to water in renal medulla.

The intramolecular negative formal charges of urea, methylurea, acetamide, 1-3-dimetylurea and thiourea were calculated by Simple-Linear-Combination of Atomic-Orbital and Molecular-Orbital Method. Then, these charges were divided by (molecular radius)2-3 or (MR-D)2-3. By this calculation, a new index showing the intensity of negative charge around the molecule was obtained. The order of the magnitude of these indices agreed well with that of ability to enhance urinary osmolality or water reabsorption in renal medulla of dogs shown by RABINOWITZ et al, and that of the accumulation strenghth of these substances into the renal medulla in anti-diuretic low-protein rats shown by TRUNIGER et al.

THE DEVELOPMENT OF SECOND-GENERATION LOW-PROTEIN RATS.

THE DEVELOPMENT OF SECOND-GENERATION LOW-PROTEIN RATS.