Interaction between pre-weaning undernutrition and post-weaning environmental enrichment on somatic development and behaviour in male and female rats

Male and female rats were undernourished from birth to 30 days by restricting access to the lactating mother, and then fed ad libitum. At weaning, underfed and normally suckled controls were permanently housed either in pairs in standard cages or in groups of 10 in 1 m³ cages containing ladders, ropes etc. Severe undernutrition during suckling followed by 4 months of refeeding, produced some changes in sexual behaviour in adult males (increased ejaculation frequency) but had no effect on behaviour in open field, dark preference or passive avoidance. Differential post-weaning environment produced significant differences in behaviour, irrespective of previous feeding conditions. Enriched animals were more active and exploratory. Females differed from males in the same direction as enriched from standard, and were more responsive to social and housing conditions.     

Effects of postnatal protein undernutrition on myelination in rat brain

Pups were subjected, from birth, to protein undernutrition by feeding the lactating dams 8% casein (CS) or 8% soy protein (SP) diet up to weaning; the weanlings were fed the same diets until 6 weeks of age. At 3 and 6 weeks of age, myelin was isolated from the brains and characterized. The quantities of myelin and its content of cholesterol, galactolipids and phospholipids, were significantly depressed in the 8% CS and 8% SP groups but not when soy protein was fed at the same level as casein (25%) in the control. Furthermore, the severity of the deficits in myelination showed a differential pattern depending on the type of dietary protein fed. At weaning, the deficits with the 8% SP diet were 1.5-2.0-times greater than with the corresponding casein diet. A more pronounced retardation in the initiation, progression and capacity of myelination in postnatal soy protein undernutrition was indicated.     

Effect of pre-weaning feeding regimens on post-weaning growth performance of Sahiwal calves

The objective of the study was to assess the post-weaning growth response of Sahiwal calves reared on four different pre-weaning dietary regimens. The four diets were: (a) whole cow's milk, starter ration (SR; CP = 20%, total digestible nutrients (TDN) = 72%) and Berseem hay (H; Egyptian clover; CP = 21%, TDN = 63%); (b) whole cow's milk + H; (c) milk replacer (MR; reconstituted to supplier specification; Sprayfo®) + SR + H; and (d) MR + H. The protein and fat percentages of reconstituted MR were 2.22 and 1.84, respectively. Milk or MR were fed at the rate of 10% of the calves’ body weight (BW) until 56 days of age, and then withdrawn gradually until weaned completely by 84 days of age. The average initial BW of calves in groups A, B, C and D were 56.3 ± 1.0, 47.5 ± 1.0, 40.4 ± 1.0 and 30.3 ± 1.0 kg, respectively. Initially, there were 12 calves in each group with six of each sex; however, one male calf died from each of groups B and C and were not replaced. During the post-weaning period, 13 to 24 weeks, the calves were fed a single total mixed ration ad libitum based on maize, canola meal, wheat straw and molasses containing 16% CP and 70% TDN. Daily feed intake and weekly BW gains were recorded. The data were analyzed by MIXED model analysis procedures using the statistical program SAS. The intake of calves as percent of their BW, feed conversion ratio and cost per kg of BW gain were not different (P > 0.05) across treatments. The daily gain at 24 weeks of age for the pre-weaning treatments A, B, C and D were 746 ± 33, 660 ± 33, 654 ± 33 and 527 ± 33 g/day and the final liveweights of calves were 119 ± 4.2, 102 ± 4.2, 95 ± 4.2 and 75 ± 4.2 kg, respectively. Gains were influenced significantly (P < 0.05) by pre-weaning treatments. The calves fed MR and H only during the pre-weaning period were unable to catch up post weaning with calves on other dietary treatments. The calves fed whole milk from birth at the rate of 10% of liveweight together with concentrates had higher weaning weight and superior growth rate post weaning as well. Thus, pre-weaning feeding was important for higher weaning weights and superior growth rates post weaning.     

Effects of post-weaning environment on learning in the rat

Rats were reared in three different kinds of post-weaning environment: (1) with litter-mates and a variety of playthings (objects/social), (2) without either litter-mates or playthings (no-objects/isolates), (3) with litter-mates, but without playthings (no-objects/social). The animals were subsequently tested on a variety of learning tasks. In one task, the rats had to remove an obstacle from an alley in order to enter a food compartment; subsequently they were required to remove the obstacle in a different way from the one they had learned. Another task was to open a door leading to a food compartment; when the rats and learned this, the floor of the apparatus was lowered so they had to reach the door by climbing a ladder. Object-deprived/isolates were slower than the objects/social group in the transfer phase of the above tasks, though not in original acquisition. Object-deprived/social animals were not inferior to an objects/social group. Isolates had a higher free feeding weight than social animals, were more active in an open field, and ran faster for food reward when deprived.     

Effect of undernutrition on DNA and RNA synthesis in subcellular fractions from different regions of the developing rat brain

The effect of undernutrition on the incorporation of [methyl-³H]thymidine into DNA and of 5-[³H]uridine into RNA of cerebral hemispheres, cerebellum, and brain stem was studied in vivo and in vitro in rats. The labeling of DNA from nuclei and mitochondria and of RNA from nuclei, mitochondria, microsomes, and soluble fractions, was also measured in vitro. The results demonstrate that nucleic acid synthesis is impaired and delayed during undernutrition. Specific effects were observed for the different brain regions and subcellular fractions: at 10 days nuclear and mitochondrial DNA and RNA synthesis was impaired, whereas at 30 days only the mitochondrial nucleic acid synthesis was affected.The delay of DNA and RNA labeling, caused by undernutrition, was most evident in the cerebellum, probably due to its intense cell proliferation during postnatal development. The specific sensitivity of mitochondria as compared to other subcellular fractions, may be due to the intense biogenesis and/or turnover of nucleic acids in brain mitochondria not only during postnatal development, but also in the adult animal.     

Purification and properties of polyphosphoinositide phosphomonoesterase from rat brain.

1. On subcellular fractionation of rat brain homogenate, polyphosphoinositide phosphomonoesterase activity was greater in the cytosol than the membranous fractions. 2. The enzyme was purified from the cytosol by column chromatography on DEAE-cellulose, calcium phosphate gel and Sephadex G-100. 3. The final preparation of the enzyme showed a 430-fold purification over the whole homogenate and appeared to be homogeneous since it gave a single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis and on isoelectric focusing. The enzyme has a relatively low molecular weight and an isoelectric point of 6.8. 4. The phosphatase showed a high affinity for triphosphoinositide. Without added Mg2+, the Km was 25 muM and V was 33 mumol Pi released/min/mg protein. 5. The enzyme hydrolysed diphosphoinositide at a slower rate than triphosphoinositide. In the presence of 10 mM Mg2+, the Km values for triphosphoinositide and diphosphoinositide were 5 muM and 25 muM respectively and V was the same for each substrate. 6. Both Mg2+ and Ca2+ activated the enzyme. While Ca2+ produced maximum activation at 100 muM, a much higher concentration of Mg2+ (10 mM) was required to elicit comparable activation. The enzyme did not show an absolute requirement for Mg2+ or Ca2+ as it exhibited low activity in the presence of 0.5 mM EDTA or EGTA. 7. The phosphatase showed maximum activity between 7.4 and 7.6. A drop in pH to 7.0 activated it almost completely, whereas an increase in pH to 8.0 halved the activity. 7.0 activated it almost completely, whereas an increase in pH to 8.0 halved the activity.     

Muscle growth during neonatal undernutrition and subsequent rehabilitation in the rat

The growth of the rat calf muscle has been followed radiographically during neonatal undernutrition and subsequent catch-up. The following observations were made: (1) The mean calf muscle width of rats reared in litters of 16 was 20% less than that of those reared in litters of 8. (2) There was no significant difference between the sexes in the degree of growth retardation brought about by suckling the pups in large litters. (3) By the end of the experiment, females had caught up in both muscle width and muscle length, the males had caught up in muscle length (identical to tibia length) but not in muscle width. (4) In male pups during undernutrition the muscle diameter was greater than in normally fed animals of the same weight (but younger). This difference was not seen in females. (5) During recovery, until a weight of about 160 g was reached, the muscle width of the neonatally undernourished rats of both sexes was less than controls of the same body weight.     

Neonatal undernutrition and RNA synthesis in developing rat brain

—Underfeeding of newborn rats results in a decreased body and brain weight at 10, 20 and 30 days of age. The DNA and RNA content of the brain in these animals are similar to those of normal controls. The in vivo and in vitro synthesis of RNA in brain is significantly decreased in undernourished rats at 10 days of age when compared with controls. The metabolic transformation of ³H-orotic acid to nucleotides is also diminished. A short period of food rehabilitation produces -an improvement in the above mentioned alterations. However, a reduced incorporation of label into microsomal RNA persists even in the last condition. The results suggest that malnutrition, during the first days of life, alters the metabolism of cerebral RNA.     

Acetylcholinesterase activity in developing rat brain during undernutrition

The effect of low protein diet on rat brain AChE activity has been studied during gestation, lactation and postweaning periods. There was decrease in enzyme activity of pups undernourished either during gestation and lactation or lactation alone, the decrease being maximum in 18-day-old pups. In postweaning rats, a significant decrease was observed after 2 and 4 weeks of undernutrition compared to the control. However, the effect of undernutrition was annuled by 2-week rehabilitation, thereby indicating that imposed undernutrition only delays the normal level of the enzyme. Moreover, it appears that the enzyme activity depends both on the nutritional status and the development age.     

Effect of undernutrition on succinate dehydrogenase and acetylcholinesterase in developing rat brain

Pups (5 days old) were undernourished by separating them for 14 hr daily from their mothers for 7, 10, 13, 16 and 20 days. The undernourished rats showed significant decrease in body and brain weight, protein and nucleic acid contents at all stages of observation as compared to controls. The activities of SDH and AChE enzymes were decreased significantly after 10 days and onwards in undernourished rat brain. However, maximum decrease in brain protein, nucleic acid contents and enzyme activities was observed during suckling-weaning-transition (20-21 days). Such alterations in enzyme activities may be correlated with the reduced oxidative and neurotransmission function in undernourished developing rat brain.     

DNA polymerase and thymidine kinase activities in different regions of rat brain during postnatal development: Effect of undernutrition

The effect of undernutrition on the activity of two key enzymes for DNA synthesis, namely DNA polymerase and thymidine kinase, in developing rat brain has been investigated. Both enzymatic activities in cerebral hemispheres and in brain stem are lower in undernourished animals than in controls at the 5th day after birth; succesively, from 5 to 30 days, they decrease in both groups of animals, however the decrease is less drastic in undernourished rats than in controls. At 30 days of age the specific activity of both enzymes is quite similar in the two groups of animals. In the cerebellum, DNA polymerase and thymidine kinase activities increase after 5 days of age showing a peak at around 9 days in controls and at about 13 days in undernourished animals, decreasing thereafter in both groups, although less drastically in undernourished animals, and reaching quite similar values at 30 days. The results obtained show that both enzymatic activities are impaired at 5 days and delayed thereafter, in agreement with the changes of DNA synthesis previously observed.     

Effect of undernutrition on some enzymes involved in the salvage pathway of purine nucleotides in different regions of developing rat brain

The effect of undernutrition on the activity of two key enzymes of purine salvage pathway, namely hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and adenine phosphoribosyltransferase (APRTase), in cerebral hemispheres, cerebellum and brain stem of rats at different days of postnatal development was studied. The activity of HGPRTase and of APRTase is significantly lower in all brain regions of undernourished animals at 5 days after birth; between 10 and 15 days of age there is a recovery of the enzymatic activity which is particularly evident in the cerebellum. Successively both enzymatic activities decrease reaching at 30 days of age values quite similar to those of controls. These results indicate that undernutrition during fetal and postnatal development, impairs and delays the activity of the enzymes of purine salvage pathway.     

Effects of anticonvulsant drugs on calcium transport and polyphosphoinositide metabolism in rat cortical synaptosomes

1. Anticonvulsants: phenytoin, phenobarbital, carbamazepine and valium at concentrations of 10-100 microM had a significantly inhibitory effect on both K+-stimulated Ca2+-uptake and 32Pi incorporation into phospholipids of rat cortical synaptosomes. 2. Other anticonvulsant, valproic acid, at concentration upto 100 microM had no effect on these two events. 3. Our results suggest that there is a link between Ca2+-influx and polyphosphoinositide turnover in synaptosomes, and this link may relate to the inhibitory effect of these drugs on neurotransmitter release mechanisms of this preparation.