Early-life Deprivation Research Articles

Impact of protein-calorie malnutrition on the developing intestine. A model in young rabbits.

We assessed the impact of protein-calorie malnutrition on the developing rabbit intestine. Litters expanded 7 days postpartum (13-16 animals) were compared to control litters (6-8 animals). Chronic nutrient deprivation in early life markedly reduced small intestinal mass, as evidenced by depressed weight, crypt-villus length, protein content and DNA content. In kinetic studies, we observed impaired mucosal growth in undernourished rabbits, as demonstrated by depressed enterocyte proliferation and epithelial migration. Intestinal maturation also appeared to be modified, as suggested by altered mucosal enzyme activities and enhanced permeability which we evaluated by measuring unidirectional Na+ transport in short-circuited Ussing chambers. These findings may contribute to the increased severity of diarrheal illness observed in clinical malnutrition in infancy.

Psychophysical assessment of visual acuity in infants with visual disorders

The measurement of visual acuity is an essential part of the eye examination of adults, but is rarely attempted in infants being examined for presumed or known eye disease. We have used a preferential looking technique to test visual acuity of infants attending a hospital eye clinic. Serial measurements of acuity of infants attending a hospital eye clinic. Serial measurements of acuity in infants with certain eye diseases can provide examples of the effects of visual deprivation on the developing human visual system. Amongst 14 cases of monocular visual form deprivation in early life, there were 9 infants who had monocular occlusion as therapy for esotropia; 3 infants who had unilateral opacities of the ocular media; and 2 infants who had unilateral eyelid closure from infection or burns. Despite differences in exact mode of deprivation, the effects on visual acuity were similar. There was a reduction of visual acuity in the deprived eye and a simultaneous increase in acuity of the non-deprived eye. These effects of monocular deprivation were not permanent. Recovery occurred with reverse deprivation or by simple cessation of the deprivation. Of 10 children with binocular visual form deprivation, there were 5 who had bilateral congenital cataracts and 5 who had bilateral uncorrected high refractive errors. Infants with cataract surgery before 2 months of age showed normal early development of visual acuity. A 4–6 month delay before treatment resulted in reduced acuity, but recovery subsequently occurred. Infants with high hyperopia or astigmatism showed no acuity deficits in the first year of life when tested with optical correction. One case of early meridional amblyopia was detected in the third year of life. After a period of optical correction there was recovery of visual acuity to normal levels. This suggests that this deficit at this age is reversible.

Ganglion cell acuity in hooded rats

Previous measurements of retinal ganglion cell acuity in hooded rats have differed significantly from behavioral tests of visual acuity. One possible source of this discrepancy is examined—that light deprivation in early life may result in deficits in ganglion cell acuity. No evidence to support this hypothesis is found. Rat retinal ganglion cells exhibit a broad range of acuities. Cells with the highest resolving capacities have acuities close to those measured previously in behavioral tests. The relationships which may potentially exist between physiological and behavioral measures of visual acuity are discussed.

The role of GABAergic inhibition in the cortical effects of monocular deprivation.

In cats and monkeys, monocular deprivation in early life results in an extensive reduction of the capability of the deprived eye to activate visual cortical cells1, apparently because of changes taking place in the visual cortex itself rather than at an earlier stage in the visual pathway2. The nature of the change taking place in the cortex is the subject of some controversy. One line of evidence favours a redistribution of the excitatory terminals relating to the two eye inputs3–5 whilst another suggests that the deprived eye input is in some way suppressed6, possibly by γ-aminobutyric acid (GABA)-mediated intracortical inhibition7. We have now sought to clarify the role of this type of inhibitory influence in monocularly deprived cats, by ascertaining whether there is an enhancement of the deprived eye input to visual cortical cells during the iontophoretic application of the GABA antagonist, N-methyl-bicuculline (NMB). Our experiments show that although intracortical inhibition may submerge the deprived eye input to some cells, it is unlikely to precipitate the cortical effects of monocular deprivation. The redistribution of excitatory terminals would seem to be a more significant factor.

Persistent Changes in Central Catecholaminergic System After Recovery of Perinatally Undernourished Rats

Pregnant rats from day 14 of pregnancy or pups were fed a control diet (24% casein) or a deprived diet (8% casein) in order to obtain the following groups: 1) Control (C-C group); 2) Prenatal deprived (D-C group); 3) Postnatal deprived (C-D group); 4) Pre and postnatal deprived (D-D group). From 50 days of age on, all groups were fed a balanced commercial stock diet until 140 days of age. A significant reduction in corporal and brain weights was observed in C-D and D-D groups during deprivation and after nutritional recovery. Twenty-four day old deprived rats showed a decrease in brain noradrenaline (NA) content but no significant change in NA concentration. By the end of the deprivation period (50 days), brain NA levels tended to be reduced or increased in postnatal deprived rats, depending upon the method of expressing the results (microgram NA/whole brain or microgram NA/g fresh tissue, respectively). At 140 days of age, i.e., after 90 days of nutritional recovery, no differences were detected between deprived and control rats. However, conversion rate of [14C]tyrosine to brain catecholamines and tyrosine-hydoxylase activity were higher in D-D rats as compared with controls at this age. These results suggest that perinatal undernutrition produces, even after a prolonged period of nutritional recovery, a permanent activation of the central catecholaminergic system in adulthood. This fact may explain the different behavioral alterations described as a consequence of protein deprivation in early life.

Undernutrition of the Merino sheep and its sequelae. V.* The influence of severe growth restriction during early post-natal life on reproduction and growth in later life

The growth of two groups of Merino lambs was severely restricted at different stages of early post-natal life so that at 420 days of age they weighed only 12 kg. When their normally grown sibs born 1 year later attained a similar weight at 53 days all groups were combined and moved to sown pastures, where they grazed together for 6½ years. During this period the ewe reproduction, growth and wool production of the experimental animals were compared. Nutritional deprivation in early life did not affect the reproduction performance of the ewes, or the birth weights and weaning weights of their progeny. The restricted lambs resumed normal growth for the first two years of the recovery period, but their growth potential was not sustained, and consequently the severe growth restrictions imposed in early life had as its sequel a smaller adult. Wool production, and the number of wool fibres per sheep, were both significantly reduced by growth restrictions in early life. ___________________ *Part IV, Aust. J. Agric. Res., , 19: 997 (1968).

Effect of Malnutrition in Early Life on Avoidance Conditioning and Behavior of Adult Rats

The influence of malnutrition in infancy upon the development of certain behavioral characteristics was investigated by studying conditioned avoidance learning and extinction in adult rats subjected to nutritional deprivation in early life. In the preweaning period, young rats suckled dams fed a low protein diet (12% casein) which suppressed milk production. At 3 weeks of age the pups were weaned and divided into 3 treatment groups. One group was fed a low protein diet (5% casein). The second group was provided a basal diet (25% casein) but in restricted amount to maintain the same body weight as at weaning. The third group was changed to the basal diet ad libitum. After 4 weeks, protein- and calorie-restricted animals were rehabilitated by feeding them the basal diet. Control rats were fed the basal diet throughout the entire experimental period. From 95 days of age, all rats were subjected to avoidance conditioning. They learned to jump on a vertical screen when a conditioned stimulus (sound) was presented. The unconditioned stimuli, shocks from electrified floor grids, occurred after presenting the conditioned stimulus for 10 seconds. Duration of the latent periods and spontaneous activity throughout the periods of observation were recorded. After 6 tests of conditioning, 1 extinction experiment was carried out. There were no significant differences between control and previously malnourished rats in the learning rate expressed in terms of the duration of latent periods, but striking behavioral disturbances developed in groups of rats which had been restricted both before and after weaning. During 12 days of the experiment, increased excitability was recorded in these rats. Behavioral abnormalities were manifested as inadequate stereotyped movements and inability to delay or to extinguish the fixed conditioned reactions. Animals restricted in the preweaning period only did not show signs of disturbances which characterized the behavior of rats restricted both before and after weaning.

Influence of Malnutrition in Early Life on Exploratory Behavior of Rats

Development of exploratory behavior during the preweaning period and the intensity of exploratory activity in adults were studied in rats subjected to nutritional deprivation in early life. In the preweaning period, the dams of experimental animals were fed a low protein diet (12% casein) to suppress milk production. Control rats were provided a well-balanced basal (25% casein) diet. At 3 weeks of age the pups were weaned and divided into 3 treatment groups. One group was fed an extremely low protein diet (5% casein), a second group was fed the basal diet in restricted amount to prevent any growth, and the third group was provided basal diet ad libitum. After 4 weeks, protein- or calorie-restricted animals were rehabilitated by feeding the basal diet. Control rats were fed the basal diet throughout the entire experimental period. Protein restriction of lactating rats soon affected growth and behavior in their offspring. Lower body weight and slower development of exploratory behavior were found in experimental animals from day 10 of life. After weaning, severe protein or calorie restriction caused an elevation of spontaneous activity in male rats and calorie-restricted females. Animals fed the low protein diet during only the preweaning period did not show increased intensity of exploratory activity in the postweaning period. After nutritional rehabilitation, exploratory activity declined rapidly in all treatment groups. At day 75 and day 85 of life, all previously malnourished rats showed a very low exploratory drive. A consistent tendency to reduce spontaneous activity was found both in the group that was malnourished only in the preweaning period and in rats that also had been restricted for 4 weeks after weaning. At day 85 of life, all experimental groups differed significantly from normally fed rats. Similar trends in behavioral changes were observed in males and in females.

Urinary diversion in congenital paraplegia.

The distinctive problems of congenital paraplegia are compared with those of the acquired form, particularly with regard to associated handicaps, renal immaturity, lack of perceptual experience and social deprivation in early life. Reference is made to the management of retention of urine and to the changing urological picture as age advances. The satisfactory management of male incontinence is discussed. Against this background are enumerated the requirements of the ideal urinary diversion. The isolated ileal loop operation, or ileocutaneous ureterostomy is discussed. A series of 70 patients is surveyed and the criteria for operation are presented in relation to pre-operative management, morbidity and mortality. Long-term follow-up data are given concerning 50 consecutive girl patients operated on between 1955 and 1963 selected for ileal loop diversion from 473 paraplegic children under observation since 1946. The operative mortality was nil. The subsequent fallout rate due to death from the paraplegia or related conditions has been seven (14 per cent.), three in the first 4 months, one in the 3rd year, two in the 4th year and one in the 10th year. Ileal loop urinary diversion is claimed to be the most satisfactory method of dealing with incontinence arising from congenital paraplegia in the female, and should not be undertaken before the age of five.

Influence of Nutritional Deprivations in Early Life on Learning Behavior of Rats as Measured by Performance in a Water Maze

Learning behavior was studied in rats that were subjected to different forms of nutritional deprivation in early life. Food deprivation during the first 3 weeks of life was achieved by increasing the number of rat pups nursing from one lactating female. At 3 weeks of age rats were weaned and some were fed an extremely low protein diet for 8 weeks. Four treatment groups were established by subjecting rats to either of these nutritional deprivations alone or by combining the 2 forms of restriction or by providing optimal nutrition from birth. When the rats were from 6 to 9 months of age, visual discrimination performance in a Y water maze was measured. Male rats that were deprived both before and after weaning made significantly more errors than the normal controls. The animals that were deprived pre-weaning or post-weaning alone gave intermediate results. No significant differences were obtained among female rats subjected to the same treatment regimens. The conclusion has been drawn that nutritional deprivation in early life can cause a long-lasting, possibly permanent retardation in the development of learning behavior. Motivational or emotional behavioral differences were noted among the treatment groups and therefore the relative contribution of “drive” as contrasted with “capacity” in the altered learning behavior is not known. When rats were tested for position reversal performance in the water maze shortly after weaning and during the time that certain groups were receiving the severely protein-deficient diet, the most errors were made by the double-deprived rats, followed closely by those that were malnourished only after weaning. Rats that had been restricted prior to weaning only or the normal controls made the fewest errors. Female rats showed a less definite effect of dietary treatment on performance than the males.