Nutritionally Small-for-Dates Rats: Their Subsequent Growth, Regional Brain 5-Hydroxytryptamine Turnover, and Behavior

Abstract

ExtractRats were subjected to nutritional growth retardation either from conception to 5 postnatal days of age (fetal and neonatal restriction ( F N R ) group), or from 5 to 25 postnatal days of age (infantile restriction ( I R ) group). The FNR group may serve a s 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-sec 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. SpeculationLasting changes have been shown here in rats undernourished a t a stage of development commonly implicated in the growth retardation of many human small-for-dates infants. It would therefore be fostered to a well nourished mother and subsequently receive a good nutrition to adulthood. These animals are referred to as the FNR group.Such FNR rats do not grow to be as large as controls, despite an early phase of partial or even complete catch-up (5, 33). Their brains are uniformly small, insofar as the three major brain regions examined show similar deficits in weight; and they probably contain fewer synapses (33). In the present study a more detailed investigation was made of the brain architecture of FNR rats.For a few days after their transfer from a low to a high plane of nutrition at 5 days of postnatal age, the FNR rats show evidence of retarded neurologic maturation, but they appear to make good these delays quite soon (5). However, there still remains the possibility of some lasting effects on behavior. In an attempt to assess some aspects of emotional behavior, observations were made during the present investigation on the behavior of adult rats in stressful situations.Early undernutrition may also have some lasting effects on brain metabolism. For example, alterations in the activities of enzymes involved in the metabolism of certain neurotransmitters have been found in adult ra...

Programming the brain: Common outcomes and gaps in knowledge from animal studies of IUGR

“…Differing types of nutrient restriction have 156 been utilised, particularly in rats, with some restricting dietary protein, while others impose global nutrient restriction accounts in part for variable reductions in birth weight (Table 2). These range 159 from 4 to 34% in progeny of globally nutrient-restricted rats [79,87,88,[93][94][95][96], whilst more severe 160 restriction is seen in models of maternal protein restriction, with 7 to 52% reduction in birth weight 161 in progeny [91,92,[97][98][99][100][101]. The reported decrease in birth weight following the levels of maternal 162 nutrient restriction used in neurodevelopmental studies in sheep and rabbits is milder ranging from 163 9.5% to 17.5% [83,89,102,103].…”

“…↓ [93] ↓ [162] = [163] Cerebrum = [79,85] ↓ [93] Midbrain ↓ [93] Hippocampus = [85,93] Cerebellum = [79,85] ↓ [93] …”

“…= [214] ↓4-23% [79,87,88,[93][94][95][96] = [201,215] ↓7-52% [91,92,[97][98][99][100][101]216] ↓9.5-14% [83,89] = [84] ↓[128, 129,131,146] ↓8-40% [99,112,114,115,160,203,217,218] ↓36-42% [145,162] ↓18-44% [102, 116-118, 163, 212] ↓42-48% [122,124,125] ↓17-28% [132,[134][135][136][137][138][139][140][141] Brain size = [214] ↓cerebrum, 11% [79] ↓11-66% [90,…”

“…Behavioural anxiety = male pups [79] =/↑ adult males [93,94] ↓ adults [98,216] ↑ reactivity to physical restraint and surprise, adults [84] ↑ adolescent females = adolescent males [131] ↑ adults [117] ↑ low birth weight female lambs [150] Spontaneous ambulation = adult males [94,95] ↑ females [165] ↑ in isolation tasks, adults [84] ↑ adults [113][114][115] ↓ adult males [160] ↓ Hyperactivity ↑ adult females [165] ↑adults [113][114][115] Exploratory behaviour ↑adult females [216] ↑adults [113][114][115] ↓ adults [117,163] Response to novelty ↓novelty seeking, adults [84] = adults [113] …”

Recognition memory and DNA damage in undernourished young rats

“…Modifications of functionality in nervous system cells due to nutrient deficiency promote changes in the processes involved in learning and memory (Valadares et al 2010). However, this fact is not fully proven because there are studies that indicate improvement in spatial memory in undernourished rodents (Smart et al 1976).…”