Janina R. Galler

Effects of prenatal protein malnutrition on the hippocampal formation.

In this review we have assessed the effects of prenatal protein malnutrition on the hippocampal formation of the developing brain. In investigating this insult in the hippocampal neuronal model we have concentrated on aspects of enhanced inhibition we have shown in our earlier studies. Since this involves particular attention to the GABAergic interneurons we have examined the complex interneuronal networks of the hippocampal formation and their neurotransmitter afferent inputs, particularly the serotonergic system from the midbrain raphé nuclei. A variety of combinations of specialized interneurons are discussed in terms of how malnutrition insults perturb function in these inhibitory and disinhibitory networks. Pathological enhancement of inhibition manifests itself by diminished plasticity, alterations in theta activity and deficits in long-term learning behaviors. Long-term inhibition in select GABA interneuron systems may form a major derangement seen following prenatal protein malnutrition. The focus of this study is to relate enhanced inhibition to the several forms of inhibitory systems present in the hippocampal formation and develop hypotheses as to the primary derangements that may account for pathological inhibition in prenatal malnutrition.

Prenatal Malnutrition-Induced Changes in Blood Pressure: Dissociation of Stress and Nonstress Responses Using Radiotelemetry

A link between prenatal malnutrition and hypertension in human populations has recently been proposed. Rat models of prenatal malnutrition have provided major support for this theory on the basis of tail-cuff measurements. However, this technique requires restraint and elevated temperature, both potential sources of stress. To determine the effect of prenatal protein malnutrition on blood pressure under nonstress conditions, 24-hour radiotelemetric measurements were taken in the home cage. Male rats born to dams fed a 6% casein diet for 5 weeks before mating and throughout pregnancy were studied in early adulthood (from 96 days of age). During the waking phase of their cycle but not the sleep phase, prenatal malnutrition gave rise to small but significant elevations of diastolic blood pressure and heart rate compared with well-nourished controls. Direct effects of stress on blood pressure responses were determined in a second experiment using an olfactory stressor. Prenatally malnourished rats showed a greater increase in both systolic and diastolic pressures compared with well-nourished controls during the first exposure to ammonia. A different pattern of change of cardiovascular responses was also observed during subsequent presentations of the stressor. These findings of a small baseline increase in diastolic pressure consequent to prenatal malnutrition, but an augmented elevation of both systolic and diastolic pressures after first exposure to stress, suggest the need to reevaluate interpretation of the large elevations in blood pressure previously observed in malnourished animals using the stressful tail-cuff procedure.

The Influence of Early Malnutrition on Subsequent Behavioral Development: II. Classroom Behavior

The classroom behaviors of 129 Barbadian children (77 boys and 52 girls) aged 5 to 11 years, who suffered from moderate-severe protein-energy malnutrition in the first year of life were compared with those observed in children with no history of malnutrition. The data were gathered from questionnaires administered to teachers who were unaware of the childs previous nutritional history. The results demonstrated that the previously malnourished children had attention deficits, reduced social skills, poorer physical appearance and emotional instability when compared to the matched comparison children. These behavioral deficits associated with prior malnutrition were independent of IQ and were experienced to a greater extent by boys. Socioeconomic conditions at the time of the study contributed little to the behavioral deficits of the previously malnourished children, as compared with the large contribution of the history of early malnutrition or the conditions producing it.

Prenatal protein malnutrition affects exploratory behavior of female rats in the elevated plus-maze test

To study the effects of prenatal protein deficiency in the exploration of the elevated plus-maze, an ethological procedure was used. Female rats were provided with 25% (control) or with 6% (low-protein) casein diets before and during pregnancy. After birth eight pups in each litter (six males and two females) were fostered to a control mother. After weaning (21 days of age) all animals received a lab chow diet until behavioral testing began at 70 days of age. Individual prenatally malnourished (n = 12) and well-nourished (n = 12) females were placed at the center of the elevated plus-maze and allowed to explore for a 5-min session. One session was given per day for 6 consecutive days. The following variables were recorded: percentage of open arm entries; percentage of time spent in open arms; total arm entries; time in the center platform; latency to first open arm entry; number of attempts to enter an open arm; number of rearings; number of head-dips. The results showed a significant effect of malnutrition on six behaviors (percent open arm entries, percent time spent in open arms, attempts to enter open arms, rearings, head-dips, and latency to first open arm entry) and a significant diet by session interaction on two behaviors (attempts to enter open arms and head-dips). These results indicate increased exploration of the open arms in prenatally malnourished as compared with well-nourished control rats, suggestive of lower anxiety and/or a higher impulsiveness in these animals.

The Influence of Early Malnutrition on Subsequent Behavioral Development: I. Degree of Impairment in Intellectual Performance

The intellectual performance of 129 Barbadian children (52 girls and 77 boys), aged 5 to 11 years, with histories of moderate to severe protein-energy malnutrition in the first year of life was compared to that of matched comparison cases with no such history, using a modified version of the WISC. IQ scores of boys and girls with a history of malnutrition were significantly lower than those of the comparison children. IQ was examined in relation to current socioeconomic conditions of the family, including degree of crowding, income and physical resources of the home. In this study, socioeconomic differences between the two groups were not significantly associated with the reduction in IQ performance. This study supports the important relationship between the early history of malnutrition and conditions associated with this event with later IQ deficits at school age.

Maternal Depressive Symptoms Affect Infant Cognitive Development in Barbados

This longitudinal study is part of a series examining the relationships between maternal mood, feeding practices, and infant growth and development during the first 6 months of life in 226 well-nourished mother-infant dyads in Barbados. In this report, we assessed maternal moods (General Adjustment and Morale Scale and Zung Depression and Anxiety Scales), feeding practices (scales describing breast-feeding and other practices associated with infant feeding in this setting), and infant cognitive development (Griffiths Mental Development Scales). Multivariate analyses, with and without controlling for background variables, established significant relationships between maternal moods and infant cognitive development. Infants of mothers with mild moderate depression had lower Griffiths scores than infants of mothers without depression. Maternal depressive symptoms and lack of trust at 7 weeks predicted lower infant social and performance scores at 3 months. Maternal moods at 6 months were associated with lower scores in motor development at the same age. Although no independent relationships emerged between feeding practices and infant cognitive development, the combination of diminished infant feeding intensity and maternal depression predicted delays in infant social development. These findings demonstrate the need to carefully monitor maternal moods during the postpartum period, in order to maximize the benefits of breast-feeding and related health programs to infant cognitive development.

Malnutrition and Reactivity to Drugs Acting in the Central Nervous System

There is a well-established body of data demonstrating that protein or protein-calorie malnutrition experienced early in life is associated with neuroanatomical, neurochemical, as well as behavioral alterations in both animals and humans. A number of studies has focused on the following question: are the neuroanatomical and/or neurochemical changes produced by early malnutrition responsible for the altered behaviors reported in malnourished animals? A tool that has been used to help answer this question is the administration of drugs with specific actions in the various neurotransmitter systems in the central nervous system (CNS). This neuropharmacological approach has produced a considerable amount of data demonstrating that malnourished animals react to drugs differently from controls, suggesting that the altered behavioral expression of these animals could be partly explained by the alterations in the brain function following malnutrition. The present review will provide an overview of the literature investigating the reactivity of malnourished animals to psychoactive drugs acting through GABAergic, catecholaminergic, serotonergic, opioid and cholinergic neurotransmitter systems. Altered responsiveness to psychoactive drugs in malnourished animals may be especially relevant to understanding the consequences of malnutrition in human populations.

A Follow-up Study of the Influence of Early Malnutrition on Development: Behavior at Home and at School

A follow-up study of home and classroom behavior was conducted on 216 children, 9 through 15 years of age, half of whom had histories of moderate-severe protein energy malnutrition (marasmus) during the first year of life. Behavior was measured by two rating scales, administered to teachers and parents of the children. Observations made by teachers and parents were significantly correlated on 33% of the 41 overlapping items in the two questionnaires. The history of malnutrition had a significant association with attention deficits in children up to 15 years reported by parents and teachers, even when the effects of socioeconomic and home environmental factors were controlled. It was concluded that interventions specifically focussed on these attentional deficits should be considered early in life for children exposed to infantile malnutrition in order to prevent behavioral disorders in adolescence.

Effects of prenatal protein malnutrition on kindling-induced alterations in dentate granule cell excitability: II. Paired-pulse measures

The effects of prenatal protein malnutrition on kindling-induced changes in inhibitory modulation of dentate granule cell activity were examined by analysis of extracellular field potentials recorded from the granule cell layer of the dentate gyrus in response to paired-pulse stimulation of the perforant pathway in freely-moving rats. Since we have shown that kindling results in enhanced synaptic transmission at the level of the perforant path/granule cell synapse (see preceding paper), we sought to determine if the kindling process might induce changes in inhibitory modulation of granule cell excitability which could be involved in the slower acquisition of the kindled state we have previously reported in malnourished animals. Beginning at 120-150 days of age, the response of dentate granule cells to paired-pulse stimulation of the perforant path was examined at interpulse intervals (IPIs) ranging from 20-1000 ms. A paired-pulse index (PPI) was constructed based on the mean percent change in population spike amplitudes of the two responses resulting from application of the pulse pair. PPI measures obtained during the kindling process were compared with individual prekindling measures to determine the mean percent change in excitatory/inhibitory modulation of granule cell activity. Significant inhibition of the second population response was apparent at all IPIs tested for both diet groups following the first kindled afterdischarge.(ABSTRACT TRUNCATED AT 250 WORDS)

The Influence of Early Malnutrition on Subsequent Behavioral Development III. Learning Disabilities as a Sequel to Malnutrition

Summary: The academic performance of 129 Barbadian children (77 boys and 52 girls), who were 5-11-yr-old and suffered moderate to severe protein-energy malnutrition in the first year of life, was compared with the performance of matched comparisons, children who had no history of malnutrition. Children with a history of malnutrition were found to have lower performance on eight out of nine academic subject areas, namely, language arts, mathematics, general science, social science, reading, health, religion, and arts/crafts. Socioeconomic factors in the backgrounds of the children were also examined. A model is presented clarifying the interrelationships of malnutrition, socioeconomic status and school performance. Reduced school performance in the previously malnourished children can be largely accounted for by deficits in classroom behavior, and, to a lesser extent by a reduction in I.Q. Current socioeconomic status is not directly involved in altering academic performance whereas the early history of malnutrition and its accompanying conditions at the time of the illness are leading contributors to altered behavioral outcome and school performance.