J.L. Smart

Vulnerability of developing brain. II. Effects of early nutritional deprivation on reflex ontogeny and development of behaviour in the rat

During the last two weeks of pregnancy and throughout lactation the food intake of a group of female rats was restricted to about half that of a control group fed ad libitum. The growth, physical maturation and behavioural development of control and undernourished male offspring were compared. At 21 days the body weight of the underfed young was only one-third that of controls. The appearance of 2 out of 3 physical features, and of 4 out of 8 reflexes was significantly delayed in the undernourished group. Generally, characteristics which normally appear in the first week of postnatal life were not significantly affected; whereas most of those appearing later were significantly delayed. When rats were 9, 13, 17 and 21 days old their behaviour in an open field was observed. Exploratory responses were first seen significantly later in undernourished young. Though they moved about the field as much as the controls, they made significantly fewer upward-directed responses on the first 3 days of testing. At 21 days most control rats were able to move round the rim of a plastic beaker to a refuge platform, a feat accomplished by only a few underfed animals.

Vulnerability of developing brain. VI. relative effects of foetal and early postnatal undernutrition on reflex ontogeny and development of behaviour in the rat

Mother rats were either fedad libitum or undernourished for much of pregnancy and throughout lactation. Their offspring were cross-fostered at birth, such that the young were nutritionally deprived during only one period, either gestation or the suckling period. The growth and development of these rats were compared with those of rats from an earlier investigation which were fully fed or undernourished during both periods. Food restriction during gestation caused a 10% deficit in birth weight, but from the fifth postnatal day the growth rate was almost entirely determined by the postnatal nutritional regime. The effect of nutritional deprivation during gestation on reflex ontogeny and the development of physical features was negligible, while that of postnatal underfeeding was highly significant with respect to most characteristics maturing after day 10. Only the appearance of certain aspects of exploratory behaviour showed evidence of being retarded by gestational restriction. Nutrition during the suckling period was a major determinant of the frequency of upward responding in the open field. Balancing ability at 21 days tended to be impaired in rats underfed during the suckling period. The results are discussed in relation to the vulnerable period hypothesis of brain growth and development and its application to the human species.

Maternal behaviour of undernourished mother rats

Abstract Undernourished mother rats were given daily meals throughout most or all of pregnancy and lactation, comprising about half the amount of a good quality diet taken by controls. Their daily pattern of nest occupation and desertion during lactation was quite different from that of controls. Retrieving tests were carried out at 4, 6, 8 and 10 days after parturition. Underfed mothers were less efficient than controls in retrieving their young on days 8 and 10, and were less likely to lick their young during the test period. They also spent much more time rearing on their hind legs. Among undernourished females the number of young retrieved was negatively correlated with duration of rearing. The significance of the differences in maternal behaviour for offspring development is discussed.

Increased thirst and hunger in adult rats undernourished as infants: an alternative explanation

1. Rats were undernourished in early life by feeding their mothers a restricted quantity of a good-quality diet throughout lactation. Their undernutrition continued postweaning from 25 to 42 d of age, after which they were fed ad lib. Control rats were well nourished at all times. 2. Behavioural assessment of thirst was carried out on adult males. These were deprived of water for 23 h/d throughout the period of testing. Compared to control rats, previously-undernourished (PU) rats pressed a lever at a higher rate in a Skinner box to gain a water reward, drank more frequently during their first 5 min in an unfamiliar cage, and tended to run more quickly down an alleyway for water. PU rats also drank more (/kg body-weight 0-75) of a quinine solution (I g/l) when this was available to them ad lib. as their only source of fluid. 3. A second group of rats was growth-retarded during gestation and the suckling and early postweaning periods. The rats had free access to food from 42 d of age. In adulthood their ad lib. food and water consumption was measured. PU males ate and drank more (/kg body-weight 0-75) than control males. 4. These results indicate that adult rats which have been undernourished in early life display increased thirst. An attempt is made to explain this finding, together with their previously-demonstrated enhanced hunger drive, purely in terms of gross anatomical and physiological differences.

Motor co-ordination and cerebellar size in adult rats undernourished in early life.

The male progeny of mother rats which had been undernourished during most of gestation and all of lactation were divided into two groups when weaned at 25 days. One group was nutritionally rehabilitated (G-L-) while the other was underfed for a further 9 weeks (G-L-W-) before nutritional rehabilitation. Despite this further undernutrition the G-L-W- rats eventually caught up in both body and brain weight with the G-L- group. Compared with control rats of the same age that had been well fed throughout life, the G-L- and G-L-W- animals had permanent deficits in body and regional brain weights. At 36 weeks rats were given two tests of motor co-ordination. They were required (a) to run backwards on a revolving drum and (b) to cross a chasm bridged by a ladder or parallel rods for a food reward. Both previously undernourished groups did consistently worse than controls of the same age or of similar body weight on two measures of co-ordination: falls from the revolving drum and stumbles on the bridge-crossing test. It is postulated that these differences indicate impaired cerebellar function in the prevously undernourished rats.

A retrospective study of the relationship between birth history and handedness at six years

Bakans hypothesis that sinistrality is caused by perinatal insult was investigated by attempting to relate the handedness of 1094 six-year-old children to many aspects of their birth history ascertained from hospital records. Handedness of the children and their families was obtained by questionnaire. A secular increase in the frequency of sinistrality was noted, from 6.2% among grandparents to 17.5% among the children. Most boys were left-handed than girls. Only two aspects of birth history predisposed to sinistrality: boys born by breech delivery and children born to primiparous mothers over 38 years old were more likely to be left-handed.

Social behaviour of rats following pre- and early postnatal undernutrition

Abstract The social behaviour of adult male rats which had been undernourished at some stage before weaning was investigated. Litters were cross-fostered at birth between well fed and underfed dams. Thus, some were undernourished only during gestation, others only during the suckling period and others throughout both periods. After weaning all animals had free access to food and were grouped with two or three littermates. Each adult previously undernourished rat was allocated its own control partner which had been well fed throughout life. Four measures of social interaction were recorded during five 10 min tests. Postnatal undernutrition increased the frequency of allogroom and walk over and pre with postnatal undernutrition had a similar effect. Rearing and mount were unaffected by either treatment. Prenatally growth restricted rats did not differ from controls on any measure. Thus, adult social behaviour was more affected by the postnatal than by the prenatal experience. In another experiment smaller control rats were found not to differ in their social behaviour from larger control rats, indicating that size is not an important factor in these studies.

Sucking behaviour and milk intake of neonates in relation to milk fat content

The hypothesis that a high concentration of fat in milk acts as a satiety signal for babies was tested by feeding neonates formula milks of different fat concentrations. Babies were tested on 2 consecutive days. On day 1 they were fed a high fat milk followed by a low fat milk, or vice versa, each for 2 min; and on day 2 the same procedure was followed but in the opposite order. Milk intake and 6 parameters of sucking behaviour were recorded. There was no indication that high fat milk acted as a cue to babies to slow or stop feeding. On the contrary babies appeared to feed more actively on the high fat milk, in that they sucked in longer bursts for it and spent a smaller proportion of the test period resting.

Social interactions among adult male rats after early undernutrition

1. Developing rats were growth-retarded during gestation and the suckling period by underfeeding their mothers from mating. After weaning, all animals were fed ad lib . 2. At 18 weeks each male was paired with another male for 10 min on 4 consecutive days. Tests 1 and 2 were with males of like-treatment group and tests 3 and 4 with males of unlike-treatment group. 3. Pairs of previously undernourished rats boxed and fought more often than pairs of controls. In the mixed pairings of tests 3 and 4 the previously underfed animals initiated contact more frequently than did their control partners. 4. Evidently there is a lasting effect of early nutritional deprivation on inter-male social behaviour, especially when both of the animals interacting are of the previously undernourished type.

Further Studies of Body Growth and Brain Development in ‘Small-for-Dates’ Rats

Rats were growth-retarded either from conception to 5 postnatal days (FNR or ‘small-for-dates’ group) or from 5 to 25 postnatal days (IR group) by underfeeding their mothers or foster-mothers. All young were fed ad libitum from weaning till they were killed at 15–24 weeks. The body weight of the FNR rats was 36% less than that of controls at 5 days and remained significantly less throughout their lives. Their adult nose-rump and tail lengths were slightly but significantly shorter than those of controls, but they did not differ in total body fat. TR rats weighed less than control and FNR rats from 10 days onwards, and they were leaner than both groups at death. They grew more in nose-rump and tail length between 35 and 115 days than the other groups, but were still significantly shorter than the controls at 115 days. This ‘catch-up’ may be related to their relative skeletal immaturity (assessed radiographically) at the time of the body growth spurt. Brain growth was impaired in both FNR and IR rats, though in different ways. Cerebellar growth was selectively affected in IR but not in FNR rats. Total synaptosomal protein (a probable measure of synapse number) was lower in the brains of both experimental groups in proportion to their brain weight deficits.