Early undernutrition: subsequent growth of male and female rats.
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Biomedical subjects
Publications and source records attributed to J Dobbing.
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The curves for biparietal diameter, head circumference and brain weight with increasing age have different shapes, and these differences have been explained. Interconversion procedures are suggested. One important consequence of changing growth velocities relates to assessing prognosis for catch-up following adversity. On the assumption that catch-up of brain growth must occur within the period of the brain weight growth spurt, the interpretation of head circumference charts is discussed.
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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.
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The growth-retarded offspring of mother rats undernourished throughout pregnancy and lactation were fed ad libitum from weaning. Males were tested at 100 days of age, and ovariectomized females at 150 days. After 2 weeks of isolation, pairs of males consisting of 1 control (C) and 1 previously undernourished (PU) rat were observed for 10 min on each of 9 consecutive days. Similarly paired and treated female rats were tested a total of 8 times, the first 3 tests being separated from the last 5 by a 10-day interval. The PU rats, whether male or female, performed more rearing responses and PU male rats ambulated more in the social situation than C rats. The PU males also performed more of the social responses allogroom, walk over, and mount than C males. Similarly, PU females performed more allogroom and crawl under than C females. In general, PU rats were more active than C rats and more socially responsive.
Five-day-old rats subjected to prolonged asphyxia at 37 degrees C show a slower rate of synthesis of 5-HT as measured by the accumulation of the amine after inhibition of monoamine oxidase. During recovery from asphyxia 5-HT synthesis is markedly stimulated when measured over a 50 or 90 min period. No change in 5-HT synthesis was observed in 5-day-old rats during recovery from cold exposure or immobilization. The results indicate that the persistent increase in synthesis that follows resuscitation may be related to asphyxia per se rather than to the stress component of the treatment.
Little is known about the affects of long-term intravenous nutrition on brain growth and development in low birthweight infants. We report the post-mortem analysis of the brain of an infant born at 32 weeks of gestation who died 10 weeks of continuous intravenous feeding. During this time there was evidence of brain growth while somatic growth was severely restricted. Compared with normal data for brain biochemistry for 42 weeks of gestational age, measurements showed that the brain was small and biochemically immature with the cerebellum and brain stem being particularly affected.
Rats were subjected to nutritional growth retardation either from conception to 5 postnatal days of age (fetal and neonatal restriction (FNR) group), or from 5 to 25 postnatal days of age (infantile restriction (IR) group). The FNR group may serve as a model for the human small-for-dates baby. At 20 weeks of age cerebellum, midbrain, and cerebrum were significantly reduced in weight by 4%, 5%, and 4%, respectively, in FNR animals when compared with controls. Only cerebellum and midbrain were affected in IR rats of the same age, but in both regions the percentage deficits (8% and 9%, respectively) were greater than in FNR animals. Both cerebellum and midbrain weighed significantly less in IR than in FNR rats. The timing of nutritional growth retardation appeared to be of little consequence to the regional brain turnover of 5-hydroxytryptamine in adulthood. The rate of synthesis in the hippocampus of both FNR and IR animals was significantly faster (67% and 75% respectively) than in controls. The increased turnover could perhaps represent "overactivity" of those 5-hydroxytryptaminergic neurons terminating in the hippocampus. Some differences in the behavior of the previously undernourished adult animals were also evident. On the fifth day of testing, control rats were most venturesome in the open field. Eighteen control rats left the edge zone within 2 min, whereas only 8 FNR and 11 IR rats did so. Most animals froze immediately after a 7-sex exposure to a loud electric bell. The delay before moving about again differentiated the three groups. FNR rats took longest to move out of the area in which they froze.
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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.
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1. Rats were undernourished in early life by feeding their mothers a restricted quantity of a good-quality diet during pregnancy and lactation. All offspring were fed ad lib. from weaning. Behavioural tests were done using adult males. 2. Thresholds of aversion to electric shock were determined in a rectangular box, one side of which was designated 'live' and the other 'safe' (o V side) for any particular shock level. Three 15 min sessions were given at each of five shock levels. Previously undernourished rats had a lower aversion threshold than controls. They spent more time than controls on the o V side at two intermediate levels of shock. 3. Other male rats were subjected to six graded series of brief, unavoidable shocks. Previously undernourished rats responded to a greater total number of shock than controls. 4. These results support the hypothesis that previously undernourished rats have a lowered threshold of arousal.
1. Treatment of pregnant rats with cytosine arabinoside (ara-C, 50 mg/kg, i.p.)at 14 days of gestation severely impaired both prenatal and postnatal whole brain growth in their offspring, although the cerebellum was relatively less affected than whole brain. 2. Rats treated at 5 days of age with ara-C (250 mg/kg, i.p.) showed an impairment in growth of the cerebellum relative to the rest of the brain. 3. Adenine arabinoside (ara-A) treatment, either prenatally or postnatally, had negligible effect on brain growth, even at doses considerably higher than those of ara-C. 4. Adult rats, previously treated with ara-C (50 mg/kg, i.p.) at 14 days of gestation, showed an impairment in discrimination learning when tested in a water T-maze. 5. These results are discussed in relation to the proposed use of ara-C or ara-A as antiviral agents, particularly against intrauterine infection with cytomegalovirus.