Effects Of Prenatal Malnutrition Research Articles

Prenatal malnutrition and lead intake produce increased brain lipid peroxidation levels in newborn rats

Objectives: Prenatal malnutrition (M) and lead intoxication (Pb) have adverse effects on neuronal development; one of the cellular mechanisms involved is a disruption of the pro- and anti-oxidant balance. In the developing brain, the vulnerability of neuronal membrane phospholipids is variable across the different brain areas. This study assesses the susceptibility of different brain regions to damage by quitar tissue oxidative stress and lead quitar concentrations to determine whether the combined effect of prenatal malnutrition (M) and lead (Pb) intoxication is worse than the effect of either of them individually.Methods: M was induced with an isocaloric and hypoproteinic (6% casein) diet 4 weeks before pregnancy. Intoxication was produced with lead acetate in drinking water, from the first gestational day. Both the M and Pb models were continued until the day of birth. Four brain regions (hippocampus, cortex, striatum, and cerebellum) were dissected out to analyze the lipid peroxidation (LP) levels in four groups: normally nourished (C); normally nourished but intoxicated with lead (CPb); malnourished (M); and M intoxicated with lead (MPb).Results: Dam body and brain weights were significantly reduced in the fourth gestational week in the MPb group. Their pups had significantly lower body weights than those in the C and CPb groups. The PbM group exhibited significant increases of lead concentration and LP in all areas evaluated. A potentiation effect of Pb and M on LP was found in the cerebellum.Discussion: This study provides information on how environmental conditions (intoxication and malnutrition) during the intrauterine period could differentially affect the development of neuronal plasticity and, in consequence, alter adult brain functions such as learning and memory.

Anatomy of corpus callosum in prenatally malnourished rats

The effect of prenatal malnutrition on the anatomy of the corpus callosum was assessed in adult rats (45-52 days old). In the prenatally malnourished animals we observed a significant reduction of the corpus callosum total area, partial areas, and perimeter, as compared with normal animals. In addition, the splenium of corpus callosum (posterior fifth) showed a significant decrease of fiber diameters in the myelinated fibers without changing density. There was also a significant decrease in diameter and a significant increase in density of unmyelinated fibers. Measurements of perimeter's fractal dimensions from sagittal sections of the brain and corpus callosum did not show significant differences between malnourished and control animals. These findings indicate that cortico-cortical connections are vulnerable to the prenatal malnutrition, and suggest this may affect interhemispheric conduction velocity, particularly in visual connections (splenium).

Spatial Learning Deficits Induced by Muscimol and CL218,872: Lack of Effect of Prenatal Malnutrition

The sensitivity of prenatal protein malnourished rats to the amnestic properties of the direct GABA<PRE>A</PRE> receptor agonist muscimol and the selective benzodiazepine (BZ) receptor agonist, CL218,872, was studied in the male offspring of rats provided with a protein deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy. At postnatal day 90, rats were tested during acquisition of the submerged platform version of the Morris water maze task using four systemic doses of muscimol (0.1, 0.3, 1.0 and 1.8 mg/kg i.p.) or three systemic doses of CL218,872 (1.0, 3.2, and 5.6 mg/kg i.p.). In a dose dependent manner both drugs impaired acquisition of the task and impaired accuracy of the search pattern on the probe trial (platform removed). However, neither drug dissociated the performance of the two nutritional groups. These data are important in light of previous findings of differential behavioral effects of the non-specific BZ agonist, chlordiazepoxide (CDP), on spatial learning and on drug discrimination in prenatally malnourished rats and in the context of previous findings of reduced sensitivity to the anxiolytic effects of non-specific BZ receptor agonists across a wide variety of models of malnutrition. The present findings also support the concept that prenatal malnutrition does not affect the global functioning of the GABA<PRE>A</PRE> receptor, but fundamentally alters the way in which a subset of GABA<PRE>A</PRE> receptors (i.e. those containing the 2, 3 and/or the 5 but not the 1 subunit) is modulated by BZs.

Effects of prenatal malnutrition on GABAA receptor alpha1, alpha3 and beta2 mRNA levels.

Exposure of pregnant rats to protein malnutrition throughout pregnancy alters the developing hippocampus, leading to increased inhibition and selective changes in hippocampal-mediated behaviors. Given that GABA mediates most inhibitory neurotransmission, we asked whether selective changes in the levels of GABA receptor subunit mRNAs might result. Quantitative RNase protection profiling of 12 GABAA and GABAB receptor subunit mRNAs show that alpha1 and beta2 decrease in the adult (P90) hippocampal formation of prenatally malnourished rats, while the levels of alpha3 are increased. Moreover, the distribution of alpha1, alpha3 and beta2 mRNAs remains unchanged in CA1 and CA3 hippocampal subfields relative to dentate gyrus. The data suggest that prenatal malnutrition produces global changes of certain GABAA, but not GABAB, receptor mRNAs in the hippocampal formation.

Effects of prenatal malnutrition on GABAA receptor alpha1, alpha3 and beta2 mRNA levels.

Exposure of pregnant rats to protein malnutrition throughout pregnancy alters the developing hippocampus, leading to increased inhibition and selective changes in hippocampal-mediated behaviors. Given that GABA mediates most inhibitory neurotransmission, we asked whether selective changes in the levels of GABA receptor subunit mRNAs might result. Quantitative RNase protection profiling of 12 GABAA and GABAB receptor subunit mRNAs show that alpha1 and beta2 decrease in the adult (P90) hippocampal formation of prenatally malnourished rats, while the levels of alpha3 are increased. Moreover, the distribution of alpha1, alpha3 and beta2 mRNAs remains unchanged in CA1 and CA3 hippocampal subfields relative to dentate gyrus. The data suggest that prenatal malnutrition produces global changes of certain GABAA, but not GABAB, receptor mRNAs in the hippocampal formation.

Electrophysiological properties of rat hippocampal principal cells are unaltered by prenatal protein malnutrition.

There is growing evidence that prenatal protein malnutrition alters the development of the hippocampal formation in rats (Morgane et al., 1993; Galler et al., 1996; Almeida et al., 1996, for reviews). Little is known, however, of the possible functional consequences of prenatal malnutrition on the physiology of principal cells in the hippocampus. We have addressed this issue by comparing the electrophysiological properties of hippocampal neurons (dentate granule cells and CA1 pyramidal cells) in slices prepared from control and from prenatally protein malnourished adult male and female Sprague-Dawley rats. We found no significant effect of the prenatal protein malnutrition insult upon a number of intrinsic membrane properties measured with whole-cell current clamp recordings, including: resting membrane potential, input resistance, and membrane time constant, or on action potential characteristics such as threshold, amplitude, and/or firing frequency. Additionally, we saw no effect of prenatal malnutrition upon extracellular measures of glutamatergic synaptic transmission such as the presynaptic fiber volley, excitatory postsynaptic potential or population spike amplitude at the perforant path to dentate granule cell synapse or at the Schaffer collateral to CA1 pyramidal cell synapse. In conclusion, we have demonstrated that prenatal protein malnutrition does not result in significant alterations of the cellular physiological properties of these two types of principal neurons in the adult rat hippocampus.

Effect of prenatal protein deprivation on postnatal granule cell generation in the hippocampal dentate gyrus.

The effect of prenatal malnutrition, produced by protein deprivation, on postnatal neurogenesis of granule cells in the fascia dentata of the rat hippocampal formation was examined by injecting tritiated thymidine on P8 and P15 and sacrificing the pups on P30, or by injecting on P30 and sacrificing on P90. The number of labeled granule cells was significantly decreased in prenatally malnourished rats injected on P8, and unaffected in those injected on P15. In contrast, the number of labeled granule cells in prenatally malnourished rats was significantly increased in animals injected in P30. The study shows that prenatal malnutrition significantly alters the postnatal pattern of granule cell neurogenesis in rat hippocampal formation and that the effect persists despite nutritional rehabilitation at birth.

Effect of prenatal malnutrition on release of monoamines from hippocampal slices

The effect of prenatal protein malnutrition on release of monoamine neurotransmitters, their precursors and metabolites, from hippocampal slices was investigated in 15, 30, 90 and 220 days old male rats. The release of dopamine and its metabolites, tryptophan, and 5-hydroxyindoleacetic acid from hippocampal slices of malnourished rats was greater than release from control slices at all ages studied. Malnutrition also significantly increased the release of normetanephrine but only in the 220 day age group. Potassium-induced depolarization increased release of tyrosine, normetanephrine and 5-hydroxyindoleacetic acid lesss from slices of malnourished than from control rats. The release of norepinephrine, normetanephrine, serotonin and 5-hydroxyindoleacetic acid increased significantly with age while the release of tyrosine, 3,4-dihydroxyphenylacetic acid and homovanillic acid decreased significantly with age. Age was also significantly associated with the effectiveness of potassium-induced depolarization in increasing release of tyrosine, norepinephrine, normetanephrine, tryptophan, serotonin and 5-hydroxyindoleacetic acid.

Effects of prenatal malnutrition and postnatal nutritional rehabilitation on CA3 hippocampal pyramidal cells in rats of four ages

The effects of prenatal protein malnutrition and postnatal nutritional rehabilitation on CA3 hippocampal pyramidal cells were investigated in rats of 15, 30, 90 and 220 days of age. Female rats week fed either 6% or 25% casein diet 5 weeks before conception. Following delivery, litters born the same day to 6% and 25% casein diet rats were randomly cross-fostered to 25% casein diet dams and maintained on that diet until sacrificed. In 288 rapid-Golgi impregnated cells, we measured somal size, length of the longest apical dendrite, number of apical and basal dendrites intersecting 10 concentric rings 38 μm apart, synaptic spine density in three 50 μm segments of the largest apical dendrite and the thorny excrescence area. Prenatal protein malnutrition produced differential morphological changes on CA3 pyramidal cells. We observed significant decreases of somal size (at 90 and 220 days of age), of length of apical dendrites (at 15 days old), of apical (in 15 day animals) and basal (in 15, 90 and 220 day animals) dendritic branching and of spine density (in 30, 90 and 220 day animals). We also found significant increases of apical dendritic branching in 90 and 220 day old rats. These results indicate that prenatal protein malnutrition affects normal development and produces long-term effects on CA3 pyramidal cells.

Cerebral amino acid changes in an animal model of intrauterine growth retardation

As part of a series of experiments to ascertain the effects of prenatal malnutrition on brain development, we measured brain amino acids in an animal model of intrauterine growth retardation (IUGR) obtained by restriction of blood supply to the fetus in utero during the last 5 days of gestation. In the present study, amino acids were measured during development by HPLC as their O-phthaldialdehyde derivatives in cerebral cortex, cerebellum and hippocampus. In rats with IUGR, significant increase of alanine (by 20% to 50%) and taurine (by 20% to 80%) were observed prior to weaning in the cerebellum and the cerebral cortex respectively. Alanine levels were also increased in hippocampus. In control animals, at birth, activities of the GABA nerve terminal marker enzyme glutamic acid decarboxylase (GAD) were found to be 32%, 17%, and 11% of adult values in cerebellum, hippocampus and cerebral cortex respectively. Two-day-old rats with IUGR had significantly lower GAD activities in all brain regions. Thus, impairment of nutrient supply to fetal brain results in selective regional abnormalities of amino acids particularly in the cerebral cortex.

Prenatal Protein Malnutrition and Maternal Behavior in Sprague-Dawley Rats

Female Sprague-Dawley rats were provided with an adequate (25% casein) or low (6% casein) protein diet, fortified with methionine, starting 5 wk prior to gestation and continuing until the birth of their pups. At birth, the offspring were fostered to well-nourished lactating dams as follows: in Experiment 1, litters contained eight prenatally malnourished pups; in Experiment 2, litters consisted of four pups with prenatal malnutrition and four well-nourished pups; control litters for both experiments contained eight well-nourished pups. In Experiment 1, the time spent in passive nursing and pup grooming was significantly higher for dams rearing previously malnourished pups than for those rearing control litters. In Experiment 2, mixed litters were groomed less frequently than control litters, but there was no significant difference between groups for any other measure. In both experiments, the prenatally malnourished pups showed similar body weight deficits relative to well-nourished pups. These findings underscore the usefulness of mixed litters in studying the later effects of prenatal malnutrition because later deficits in brain function are less likely to be attributable to changes in the early rearing environment.

Effects of prenatal malnutrition on development of oral tissue in neonatal rats.

The effects of prenatal malnutrition on the growth of incisor and molar tooth germs and tongue were investigated in newborn rats. Compared with the results on the young of well-nourished mothers, the young of the malnourished animals had fewer and smaller cells in the molar tooth germs and fewer cells in incisor tooth germs. The tongue of the malnourished animals had fewer but larger cells. 45Ca uptake studies and alkaline and acid phosphatase activities suggested that prenatal malnutrition affected incisor and molar tooth germs in different ways. Alkaline phosphatase activity in the tongue did not differ between dietary groups. The results indicate that an adequate protein intake is extremely important for the healthy development of the teeth and tongue of the offspring.

Effect of prenatal malnutrition on cortical reactivity of the rat parietal association area.

The influence of prenatal malnutrition on the reactivity of the rat parietal association cortex was studied by testing thresholds of direct cortical responses. Chronic and acute prenatal starvation caused a significant increase of cortical chronaxy values, indicating a detrimental effect on the axodendritic synapses. Since these synapses subserve cortico-cortical influxes underlying association processes, this detrimental effect could be correlated with behavioral and learning deficits found in malnutrition.

The effect of prenatal malnutrition on dimensions of cerebral cortex

The effect of prenatal malnutrition on dimensions of cerebral cortex