Effects Of Early Undernutrition Research Articles

Maternal Response of Perinatally Underfed Wistar Virgin Females Exposed to Newborn Rats

Nutrition plays a major role in the survival of the progeny, and its perinatal deficiencies delay physical development and interfere with social and cognitive performance later in life. The effects of early undernutrition on maternal social performance of sensitized adult virgin rats were evaluated. Several maternal and non-maternal responses were measured in virgin female Wistar rats randomly divided into two groups, control and early undernourished, during 19 days of chronic daily exposure to fresh foster pups in home-cage conditions. Underfed females (F0) received different percentages of a balanced diet during gestation. After birth, pups were underfed (F1) by alternating every 12 h between litters two lactating dams, one with ligated nipples. Weaning was at 25 days of age followed by an ad lib diet until postpartum day 90, when sensitized virgins were maternally tested daily for seven successive sessions. Significantly (p < 0.05) low body weight scores in UG F1 virgins of five different ages were observed. The UG F1 females expressed significantly (p < 0.05) lower frequency values in sniffing, licking, retrieving, crouching, and handling shavings, with clear prolonged sniffing, retrieving and handling shaving latencies towards the foster pups compared with CG F1 sensitized females. Self-grooming was not affected, whereas exploration was significantly reduced. Current findings suggest that perinatal undernutrition interfered the organization of a core neuronal circuitry underlying the mother-litter interactions involved in social and cognitive performance of sensitized adult virgins. Furthermore, the behavioral maternal alterations in F1 virgins may possibly generate a risky negative social environment to induce cognitive and/or brain disorders in later generations.

Effects of postweaning undernutrition on exploratory behavior, memory and sensory reactivity in rats: Implication of the dopaminergic system

The effects of early undernutrition on behavior and brain biochemistry were examined in rats. At weaning, rats were provided either an ad lib diet (control group) or maintained at 80% of the weight of their control littermates (undernourished group). Three weeks into the diet they were tested in an open field. After 6 weeks of diet, HPLC analyses were conducted on sample brains from each group to assess levels of dopamine and metabolites, respectively dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. At seven weeks of diet, remaining rats were trained in an 8-arm radial maze, and a retention test conducted 72 h after attaining the learning criterion. At fourteen weeks of diet, sensory reactivity was measured by tail-immersion in a water bath maintained at constant temperature 50 ± 1 °C. Undernourished rats exhibited hyperactivity and increased exploratory behavior in the open field, as well as increased sensory reactivity in the tail flick test. In the radial maze, however, undernourished rats did not differ from controls in either learning or retention. Haloperidol (i. p. injection) impaired retention by control but not undernourished animals. HPLC analyses showed an increase in dopamine turnover in the striatum of undernourished rats. Our results suggest that, unlike its effects when induced immediately at birth or in adulthood, undernutrition at weaning does not appear to influence learning and retention but induced an hyperactivity and alterations in striatal DA turnover which was associated with a decrease in responsiveness to i. p. haloperidol injection.

Developmental regulation and effect of early undernutrition on phosphorylation of rat cortical synaptic membrane proteins

Undernutrition during early postnatal life was employed in rats by restricting the feeding time. The synaptic membrane fraction from cerebral cortex of normal and undernourished rats of various ages was prepared and endogenous protein phosphorylation studied. Many of the synaptic membrane proteins were found to be phosphorylated in an age-dependent manner. Early undernutrition affects the phosphorylation of various proteins in a complex way; most affected were 48-, 52-, 61- and 74-kDa proteins. These proteins were found to have phosphorylations mainly at tyrosine residues. This finding indicates that tyrosine phosphorylations may be affected most by early undernutrition. Adequate nutrition after early undernutrition removes most of the effects of undernutrition on synaptic protein phosphorylation. To address the question of how undernutrition may affect protein phosphorylation, we studied the lipid content of synaptic membrane fraction as it can affect membrane properties, including the fluidity. We found that undernutrition affects phosphorylation of most of the synaptic membrane proteins in the same manner in which it affects the cholesterol–phospholipid ratio of synaptic membrane and, hence, the fluidity of the membrane. This indicates that lipid biosynthesis is one of the ways by which undernutrition can affect synaptic membrane protein phosphorylation.

The development of locomotion in the rat

The development of free walking was studied in rats between postnatal days 10 and 20. Spontaneous quadruped walking with the ventral surface of the body off the floor was first observed at postnatal day 11. Locomotion remained clumsy and invariably slow during the next few days, but a rapid transformation into the mature pattern of locomotion occurred around postnatal day 15. This transformation involved changes in quantitative parameters of locomotion as well as a change in the movement pattern of the hindlimb. A swimming-like movement characterized by abduction, rotation and hyperextension of the paw was replaced by the digitigrade adult pattern without marked rotation. Joint angle trajectories of the major joints during the step cycle changed considerably during the transitional period. The results, which are to serve as a framework for ongoing research into the effects of early undernutrition and movement restriction upon motor function, are discussed in the perspective of developmental changes in the nervous and musculoskeletal system.

Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats

The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS.

Effects of early life undernutrition in artificially-reared rats: 3. Further studies of growth and behaviour

Four groups of rat pups were reared: mother-reared control (well-fed) and undernourished (MRC, MRU) and artificially-reared control and undernourished (ARC, ARU). AR rats were fed expressed rats' milk (days 5–7), mixtures of rats' milk and milk substitute (days 8–16), and milk substitute only (days 17–20) by intermittent infusion via a gastric cannula. Undernutrition, imposed from 5–25 days, was effected initially by underfeeding the mother (MRU) or by infusing restricted quantities of milk (ARU). Weaning was at 21 days and undernutrition from 21–25 days was by restricting the supply of solid food. All rats were fed ad lib from 25 days. From 18 weeks, male rats were subjected to 3 tests of behaviour: spontaneous alternation, conditioned food preference, and visual discrimination (Lashley stand). There were negative effects of both undernutrition and artificial rearing on body growth in weight and length. For two aspects of behaviour, preference for carbohydrate relative to protein (greater in U rats) and latency to jump (longer in U rats) the effects of early undernutrition were the same in both MR and AR animals. Hence, these effects cannot have been mediated through alterations in maternal care.

Effects of early under-nutrition on dietary self-selection and relative carbohydrate- and protein-conditioned preferences

Rats were either under-nourished from birth to 45 days and thereafter well fed, or were well-nourished throughout. Such previously under-nourished rats (PU) had a body weight deficit in adulthood of about 15% when compared with the well-fed group (C). On four training days, rats were presented with a distinctively odourized solution of carbohydrate or protein, following a 5-h period of food deprivation. On the test day, under the same food deprivation conditions as occurred during training, identical solutions distinguished only by their odour were presented simultaneously to the rats for a period of 20 min. PU rats showed a conditioned preference for the carbohydrate-paired odour. Control animals showed a small preference for the protein-paired odour. The same rats were later allowed to self-select from three macronutrients for a period of 8 days. No differences in dietary self-selection patterns were found between PU and C rats.

Effects of early undernutrition and handling on the adrenocortical activity of neonatal rats.

Early neonatal experiences such as handling or undernutrition may alter developmental patterns associated with brain maturation and neuroendocrine regulation. Therefore, we tested neonatal ACTH and corticosterone responses to ether stress in pups submitted to chronic underfeeding which involves daily handling (U), daily handling only (H), or no handling (I). Pituitary ACTH content and brain myelin basic protein (MBP) content were measured in all rat groups. We found that the order of magnitude in stress-induced ACTH secretion was: I greater than H greater than U on day 14 and 18 of age while on day 10, only a small significant response in the H group was observed. Corticosterone secretion after stress was increased on day 14 in both H and I rats while no response was observed in the U group at all ages. Pituitary ACTH content of U pups was significantly (p less than 0.01) reduced compared to H rats on day 10 of age but not later. Underfeeding had profound effects on MBP synthesis of U rats since brain MBP content on day 14 was 5-fold lower in U versus H pups. In addition, handling enhanced MBP production since H rats exhibited higher (p less than 0.05) MBP content as compared to I rats. Thus, both handling and undernutrition experienced early in life are able to affect central brain maturation as well as neonatal adrenocortical responses to stress.

Comparison of the effect of early undernutrition imposed by two different methods on rat cerebellar development

Comparison of the effect of early undernutrition imposed by two different methods on rat cerebellar development

Preferential effect of early undernutrition on rat cerebellar cholesterol and phospholipids

Preferential effect of early undernutrition on rat cerebellar cholesterol and phospholipids

Effects of nutritional supplementation on children's responses to novel, frustrating, and competitive situations

The effects of caloric supplementation for pregnant women and children from an endemically malnourished population on children's school age behavior were examined. The child's abilities to respond to routinely stressful problem-solving situations and to interact appropriately with peers were the dependent variables. Seventy-eight boys and 60 girls in rural Guatemala received different amounts of food supplementation, pre- and postnatally, as part of the INCAP Longitudinal Study. Children were classified as High or Low Supplementation, based on supplemental caloric intake prenatally and from birth to four years. When measured at 6 to 8 yr, High Supplementation children showed more interest in and exploration of a novel environment, more involvement in a competitive game, greater persistence on a frustrating task, better motor impulse control, and greater initiative across several group tasks than did Low Supplementation children. In free play with peers, the High Supplementation children showed more frequent happy affect, social involvement, and moderate activity level, and were less frequently timid or anxious. Results are consistent with findings from studies on the effects of early undernutrition on infant behavior, and suggest that behavior impairments associated with early undernutrition have long-term consequences for the child's development.

Early undernutrition and [3H]gamma-aminobutyric acid binding in rat brain.

The effect of early undernutrition and dietary rehabilitation on [3H]gamma-aminobutyric acid ([3H]GABA) binding in rat brain cerebral cortex and hippocampus was examined. Undernourished animals were obtained by exposing their mothers to a protein-deficient diet during both gestation and lactation. Saturation analysis of [3H]GABA binding in the cerebral cortex and hippocampus revealed high- and low-affinity components in the undernourished group, whereas control animals possessed only a low-affinity site. The concentration of low-affinity binding sites was greater in the undernourished animals. Rehabilitation of undernourished animals completely abolished the binding site differences. Treatment of brain membranes with Triton X-100 yielded two binding components in both the undernourished and control animals, although the concentration of lower affinity sites was still greater in the undernourished group. Neither the efficacy nor the potency of GABA to activate benzodiazepine binding in cerebral cortex was modified by undernutrition. These data suggest that early undernourishment modifies the characteristics of [3H]GABA binding, perhaps by reducing the brain content of endogenous inhibitors of the higher affinity binding site. The lack of effect on GABA-activated benzodiazepine binding suggests the possibility that neither the high- nor the low-affinity GABA binding sites are coupled to this receptor component.

Effect of early undernutrition on reactivity of the rat parietal association area

Cortical reactivity of parietal association area was studied in normal and undernourished rats. (i) The normal group was from mothers which were fed a 21.5% protein diet during lactation. (ii) The undernourished group was from mothers which were fed a 6.5% protein diet during the same period. At 21 days of age (weaning age) all animals received the same diet as that fed to the normal group. At 45 days of age, cortical chronaxie and fatigability of direct cortical responses were evaluated. The results showed that postnatal malnutrition induced alterations on cortical reactivity of that area.

Effects of early undernutrition on hippocampal development and function.

The possibility of a "hippocampal syndrome' was investigated in mature animals whose mothers had received a period of undernutrition during pregnancy and throughout lactation. Spontaneous alternation behaviour was abolished, and performance was found to be at chance level. Significant depletions in cell numbers were found throughout the hippocampal region; however, hippocampal theta rhythm remained and threshold levels for theta driving appeared normal. It was concluded that the behavioural differences observed did no arise from some simple deficit in the circuitry controlling hippocampal theta rhythm and that it was more likely due to an impairment at the synaptic level. The similarity of these, and other recent behavioural observations, to those of animals with hippocampal damage may provide a reasonable basis for investigating a number of learning deficits induced by early undernutrition.

Effects of early undernutrition and subsequent rehabilitation on acetylcholine levels in rat brain.

Early undernutrition, induced by feeding mothers a low protein (5%) diet during gestation and/or lactation, resulted in significant deficits in acetylcholine concentration in the rat brain, and these deficits were reversed by subsequent dietary rehabilitation.

Effects of early undernutrition on dendritic spines of cortical pyramidal cells in the rat.

Restricted food intake in male rats between birth and 20 days of age reduced the density of spines of layer V pyramidal cells in the frontal, parietal and occipital cortices. The loss of dendritic spines was more marked in pyramidal cell areas receiving projections from nonspecific multisynaptic systems than in cell areas associated with specific afferent systems or in areas receiving callosal projections. It was suggested that the differential effect of undernutrition in nonspecific, specific and callosal afferent projection areas of the pyramidal cortex might be related to the impairment of brain integrative functions reported to follow perinatal undernourishment.

DNA and DNases in normal and undernourished rat brain.

Earlier studies from our laboratory [Shrivastaw and Subba Rao, 1975; Subba Rao and Shrivastaw, 1976] have indicated a positive correlation between cell proliferation, as indicated by DNA synthesis, and the levels of DNases in developing chick brain. Since undernutrition is known to affect cell proliferation in developing brain, those studies are now extended to see the effect of early undernutrition on the levels of DNA and DNases along with RNA and protein in developing rat brain. Early nutritional deprivation resulted in lesser amounts of DNA, but the concentration of DNA per gram of brain did not alter. DNA, RNA, and protein values in brains of those rats undernourished from birth to 14 days but subsequently rehabilitated up to 130 days, exhibited complete recovery, while rehabilitation up to 50 days did not show full recovery in the case of DNA. Both the specific activity and total activity of acid and alkaline DNases showed significant reduction in 14-day-old undernourished brain. However, with continued nutritional restriction up to 24 days, the specific activity of these enzymes returned to normal, although the total activity was still in deficit. These results, coupled with those on DNA levels, indicate that a compensatory mechanism may come into play when developing brain is exposed to caloric restriction.

Effects of early undernutrition on motivation and discrimination learning in rats.

Offspring were either adequately nourished or undernourished during the suckling period. They had free access to food from weaning, and were given 2 behavioral tests between 13 and 19 weeks of age. Motivation for water was tested on a variable interval (VI) schedule at 3 levels of deprivation and a test of light-dark discrimination made at 23.5 hr of water deprivation. The results indicated (1) no clear difference in VI response rate, but (2) significant differences in discrimination performance between the 2 groups. A learning ability or certain relevant abilities rather than motivation for water appeared responsible for the difference in discrimination learning.

Effects of early undernutrition on motor coordination in the adult rat

Female Wistar rats were undernourished during most of gestation and all of lactation. Body weights of offspring were significantly different at 3 and 25 days and at 20 weeks. At 20 and 22 weeks animals were given a motor coordination test. Significant differences between control and experimental animals were found on both occasions. Both groups showed a significant improvement in performance within the first test period thus masking any effects of fatigue. Control animals showed a further improvement in performance after the 2-week interval and only minimal signs of fatigue. Experimental animals failed to show any further improvement and also suffered a greater degree of fatigue. Females appeared to be less severely affected in their performance. Selective deficits in skeletal muscle weights were also found with fast muscle being the most severely affected. It was concluded that performance deficits resulting from early undernutrition were in part due to skeletal muscle changes as well as cerebellar disfunction previously observed.

Effects of early undernutrition on individual cerebellar lobes in male and female rats

Effects of early undernutrition on individual cerebellar lobes in male and female rats