Effects Of Postnatal Lead Exposure Research Articles

English

This study examined the effect of post-natal lead exposure on the hippocampus of developing Wistar rats. Nine pregnant Wistar rats were randomly distributed into three groups of three rats each, consisting of a control Group 1 which received distilled water and experimental Groups 2 and 3 orally administered with 60 and 90 mg/kg bwt of lead acetate, respectively. The pups of the experimental Groups 2 and 3 were exposed to lead acetate via lactation from dams that were administered lead acetate from post-natal day (PND) 1 - PND 21. On PND 22, all the pups were weighed, and then euthanized. The brains of the pups were excised, weighed; lead deposit was quantified and fixed in Bouin’s fluid. The results revealed a significant (p 0.05) decrease in brain weight, significant increase(p<0.05) in brain somatic index (BSI), significant increase(p<0.05) in lead deposition, weak staining for Nissl substance and distortion in cytoarchitecture of the hippocampus of Wistar rat’s pups exposed to lead acetate compared to the control. Post-natal exposure to lead acetate via lactation caused an increase in lead deposition, decrease in body weight and distortion in the cytoarchitecture of the hippocampus of developing Wistar rats. Key words: Lead acetate, hippocampus, post-natal, lactation.

Assessment of the effect of post-natal lead exposure on the hippocampus of developing wistar rats

This study examined the effect of post-natal lead exposure on the hippocampus of developing Wistar rats. Nine pregnant Wistar rats were randomly distributed into three groups of three rats each, consisting of a control Group 1 which received distilled water and experimental Groups 2 and 3 orally administered with 60 and 90 mg/kg bwt of lead acetate, respectively. The pups of the experimental Groups 2 and 3 were exposed to lead acetate via lactation from dams that were administered lead acetate from post-natal day (PND) 1 - PND 21. On PND 22, all the pups were weighed, and then euthanized. The brains of the pups were excised, weighed; lead deposit was quantified and fixed in Bouin’s fluid. The results revealed a significant (p 0.05) decrease in brain weight, significant increase(p<0.05) in brain somatic index (BSI), significant increase(p<0.05) in lead deposition, weak staining for Nissl substance and distortion in cytoarchitecture of the hippocampus of Wistar rat’s pups exposed to lead acetate compared to the control. Post-natal exposure to lead acetate via lactation caused an increase in lead deposition, decrease in body weight and distortion in the cytoarchitecture of the hippocampus of developing Wistar rats. Key words: Lead acetate, hippocampus, post-natal, lactation.

Differential Effect of Postnatal Lead Exposure on Gene Expression in the Hippocampus and Frontal Cortex

Although developmental lead exposure is known to have detrimental effects on a variety of cognitive functions that depend on the integrity of the hippocampus and frontal cortex, little is known about how low levels of lead exposure affect expression of key families of genes in these structures. The present study examined the effects of exposure to environmentally relevant levels of lead during the sensitive early post-weaning period in the rat on the expression profiles of a select number of neurobiologically relevant genes (i.e., genes for neurotrophic factors, NMDA receptors, metabotropic glutamate receptors, synaptic function/plasticity, cell signaling, and transcription/regulation) in the rat hippocampus and frontal cortex. Exposure to lead (180 and 375-ppm lead acetate in food for 30 days) significantly increased blood lead levels (5.8 to 10.3 μg/dl) and significantly affected expression of many of the genes examined. In many instances, lead exposure had different effects on the same gene depending on the brain region in which the expression of that gene was examined. Gene expression in the frontal cortex was often more sensitive to modification than gene expression in the hippocampus. These results suggest that even past infancy, exposures to low levels of lead can have significant effects on gene expression in the frontal cortex and the hippocampus with the potential to exert long-term effects on behavior and cognition.

Neuromotor and Behavioural Effects of Postnatal Lead Exposure Below 10 μg/dl Among Inuit Preschoolers

Neuromotor and Behavioural Effects of Postnatal Lead Exposure Below 10 μg/dl Among Inuit Preschoolers

Inhibition of Progenitor Cell Proliferation in the Dentate Gyrus of Rats Following Post-Weaning Lead Exposure

Although lead is a potent developmental neurotoxin, the effects of postnatal lead exposure on progenitor cell proliferation in the hippocampus has not been examined. Postnatal day 25 rats were fed a lead containing diet (1500 ppm lead acetate) for 30–35 days and administered bromodeoxyuridine (BrdU, 50 mg/kg, i.p.) during the last 5 days of lead exposure. Animals were killed 24 h after the last BrdU injection. Proliferation of new cells in the subgranular zone and dentate gyrus was significantly decreased in lead-exposed rats compared to control animals that ate a similar diet devoid of lead. These results suggest that postnatal lead exposure can have significant deleterious effects on progenitor cell proliferation and thus the structure and function of the hippocampus.

Neurodevelopmental effects of postnatal lead exposure at very low levels

This study is among the first to examine specific neurobehavioral deficits in children exposed at very low lead levels. A systematic analysis for the presence of a threshold of lead exposure was conducted. The sample consisted of 246 African American, inner-city children from whom blood lead concentrations were assessed at 7.5 years of age. The results consistently show neurobehavioral deficits in relation to low levels of lead in the areas of intelligence, reaction time, visual–motor integration, fine motor skills, attention, including executive function, off-task behaviors, and teacher-reported withdrawn behaviors. Effects were identified in the specific domains of attention, executive function, visual–motor integration, social behavior, and motor skills, which have been previously suggested as part of lead's “behavioral signature”. Visual inspection of nonparametric regression plots suggested a gradual linear dose–response relation for most endpoints. No threshold discontinuity was evident. Regression analyses in which lead exposure was dichotomized at 10 μg/dl were no more likely to be significant than analyses dichotomizing exposure at 5 μg/dl. Given that associations were found between lead levels as low as 3 μg/dl for multiple outcomes, these data provide additional evidence that there is no apparent lower bound threshold for postnatal lead exposure.

Dendritic Alterations of Cerebellar Purkinje Neurons in Postnatally Lead-Exposed Kittens

Many investigations have sought to determine the effect of lead exposure on the development of the cerebellum. This study addresses the effects of postnatal lead exposure in kittens on dendritic development of Purkinje cells. Golgi-Cox filled cells were used to measure dendritic branching patterns, spine density, height, width and distance from the cerebellar surface. The results revealed a significant increase in spine density and altered patterns of dendritic branching. Complex dendritic branching was evident with a progressive shift in peak branching peripherally. Lead-exposed Purkinje cells showed early sprouting with subsequent pruning. At 5 weeks of age dendritic branches on experimental cells were increased along the entire dendritic extent. Control Purkinje cells showed initial sprouting with subsequent pruning. Normal developmental growth spurts and lead-induced effects were evident on dendritic height, width and distance from the surface. Cerebella stained with hematoxylin and eosin and cresyl violet acetate showed no evidence of vascular damage or other pathologies. These findings corroborate the evidence of hyperspiny dendritic formation representing an important mechanism of neuronal plasticity. In regard to morphological effects of lead on rodents, the hyperspiny Purkinje cell dendrites and patterns of dendritic growth in lead-treated kittens offer an alternative interpretation of neurobehavioral findings of lead-burdened children. The results are discussed with reference to other aspects of lead exposure and neural development.

Alterations in Central Monoamine Systems after Postnatal Lead Acetate Treatment in Rats

The present study was undertaken to investigate the effects of postnatal lead exposure on central monoamine systems. Newborn male Sprague-Dawley rats were given 1 or 8 mg/kg lead acetate intraperitoneally for 20 days postnatally. Two groups of control rats received sodium acetate, or sodium acetate in oversized litters to compensate for lead-induced malnutrition in the high lead dose group, while nontreated animals also served as controls. At Day 21 or 51 regional tissue levels of monoamines were determined using HPLC techniques. No major changes were seen after the lead exposures in the levels of dopamine, noradrenaline, and serotonin, or metabolites of dopamine and serotonin, when compared to respective control groups. On the other hand, in the control group given sodium acetate in oversized litters some alterations of the monoamine levels were observed in frontal cortex and striatum at Day 21 compared to controls. At Day 51, the striatal homovanillic acid and 5-hydroxyindoleacetic acid levels were higher in the low lead dose group compared to those in the controls. No other changes in the monoamine levels were seen at Day 51. At 50-70 days postnatally, potassium-stimulated dopamine overflow was studied in striatum with in vivo chronoamperometry. In the high lead dose group the amplitudes of signals were lower in both the dorsal and ventral striatum compared to the controls, while no difference was seen in the clearance time of dopamine. The capacity of the dopamine terminals to respond to repeated stimulation was not affected by the lead exposure. Thus, the steady-state levels of monoamines were essentially unaltered after postnatal lead exposure in rats, while functional aspects of striatal dopamine transmission were affected after exposure to the higher dose of lead. These findings support the hypothesis that lead-induced changes in motor skills and exploratory behavior may be related to altered dopamine neurotransmission.

Postnatal lead exposure affects motor skills and exploratory behavior in rats

The present study was undertaken to investigate the behavioral effects of postnatal lead exposure. Newborn male Sprague-Dawley rats were given 1 or 8 mg/kg lead acetate intraperitoneally daily for 20 days. Control rats received 1 mg/kg sodium acetate, or 8 mg/kg sodium acetate in oversized litters. The high dose lead acetate group and the high dose, oversized sodium acetate group showed impaired weight and length increment during the end of the treatment. Rats treated with the higher dose of lead showed delayed eye opening. The time required to turn in a negative geotaxis test was transiently longer in rats treated with the higher dose of lead. A tendency of reduced forepaw grasping ability was seen in lead-treated rats during the end of the lead exposure. Ambulation and rearing in an open field were lower for the rats treated with the higher dose of lead acetate during certain periods of development. Impaired performance in a balancing rod test was also seen in the rats treated with the higher dose of lead at the adult stage, while no difference was seen in ambulation or gnawing activity during tail pinch-induced stress. Thus, lead intoxication in rats during the early postnatal period, with doses that approximate those in children, induced transient as well as persistent dysfunctions in exploratory behavior and motor skills. These observed actions of lead may be related to impaired maturation of sensitive brain regions which develop postnatally.

Effects of postnatal lead exposure on open field behavior in monkeys

Nursery-reared rhesus monkeys were treated with either no lead or moderate levels of lead from day eight or nine until day 365 after birth. All subjects were at or below 5 μg/dl blood lead levels for at least 1.5 years by the time of the present study conducted at 4 years of age. Data were collected in a primate version of the open field test which proved sensitive to several behavioral alterations in the lead-treated monkeys. These significant differences included a failure to habituate as evidenced by number of sectors entered, increased durations of activity and environmental exploration, and a longer latency to enter the open field. Most of these effects were compatible with a hypothesis of hippocampal dysfunction in the lead-treated monkeys and appeared to indicate enduring lead-induced alterations. These results provide further support for a correlation between early lead exposure and hippocampal dysfunction. Additionally, the utility of a primate version of the open field test for behavioral toxicological studies is substantiated.

Perturbation of a hippocampal zinc-binding pool after postnatal lead exposure in rats

Morphologic alterations of the hippocampal mossy fiber pathway after postnatal lead exposure have been observed in rats. It is hypothesized that lead might perturb zinc pools found in this pathway. To test this hypothesis, rat pups were exposed to lead indirectly by administering 0.2% lead acetate to dams via the drinking water during lactation for 21 days and control litters were maintained on tap water. To evaluate whether or not the effects of postnatal lead exposure were selective for hippocampal zinc pools, the hippocampus was compared with the cerebellum. There were no significant differences between lead-treated and control rats in total zinc content in either the hippocampus or the cerebellum in rats at 30 and 90 days of age. Furthermore, no differences in the subcellular distribution of zinc were observed between control and lead-treated animals. Because the effects on zinc content may be more subtle, the amounts of cytosolic zinc-binding species, isolated using Ultrogel AcA 34 gel chromatography, were measured in control and lead-treated animals. A striking decrease was observed in the amount of zinc associated with one of the cytosolic zinc-binding species, a putative zinc-glutathione complex, shown in previous studies to be the major hippocampal zinc pool. This effect was observed only in the hippocampus of 30-day-old lead-treated rats. By 90 days of age, the effect was no longer present. These data suggest that lead preferentially affects a zinc pool found in the hippocampus and supports our hypothesis that postnatal lead exposure results in an alteration in hippocampal zinc.

Morphometric effects of postnatal lead exposure on hippocampal development of the 15-day-old rat

Neurotoxic sequelae of developmental lead exposure suggest that the hippocampus may be affected. Therefore, rats received low-level lead exposure via the milk of dams drinking 0.2% lead acetate beginning at parturition, and mid-dorsal sections of the hippocampus and dentate gyrus (DG) from 15-day-old pups were examined by light and electron microscopy. Lead exposure did not reduce body weight nor produce obviously abnormal vascularity or signs of cytotoxicity in the hippocampal formation, and total numbers per section of dentate granule cells or CA3 pyramidal cells were not reduced. On the other hand, lead exposure reduced neuropil development as evidenced both by reduced areas of the dentate hilus and dentate infrapyramidal stratum moleculare and by increased number of hilar CA3 pyramidal cells per unit area. Also, lead exposure reduced numbers of several types of synaptic profiles per unit area in the suprapyramidal mossy fiber zone. Complex invaginated (CI) profiles, assumed to be mature mossy fiber boutons, were characterized by multiple membrane densities and deep invaginations around dendritic spines of pyramidal cells. Complex noninvaginated (CN) boutons exhibited bag-like profiles with multiple membrane densities. Smaller, less numerous, simple (S) profiles contacted either dendritic trunks (ST) or spines (SS). Lead exposure reduced the numerical density of CN, CI and SS profiles in the deep (close to stratum pyramidale) part of the proximal (close to DG) region of the suprapyramidal mossy fiber zone, but did not alter the numerical density of any of the profiles in the superficial (distal to stratum pyramidale) parts of either proximal or distal (close to CA1) regions. Average size of CN profiles in the distal region was increased by lead exposure. The pattern of effects suggests that low-level lead exposure during development preferentially affects later developing structures within the hippocampal formation, rather than affecting mature structures.

Behavioral effects of postnatal lead exposure: Possible relationship to hippocampal dysfunction

A review of previous evidence suggested the possibility of hippocampal involvement in the behavioral changes observed following postnatal lead (Pb) exposure. To further assess this possibility, Long—Evans hooded rat pups were exposed to inorganic Pb from postnatal Days 1 to 25 via the maternal milk. Mothers were fed diets containing either 4.0% PbCO 3 , 0.4% PbCO 3 , or a 2.2% Na 2 CO 3 control diet throughout this period. Animals were tested at maturity in four situations considered sensitive to hippocampal dysfunction. Exposure to Pb resulted in delayed acquisition of the radial eight-arm spatial maze, but produced no changes in either the susceptibility to audiogenic seizures or the acquisition and performance of a two-way active avoidance response. Pb-exposed animals were also observed to perform deficiently on a DRL-20 schedule of operant reinforcement, although significant variation was observed between litters in the Control group on this task. The results of this study are discussed in terms of a relationship between postnatal Pb exposure and hippocampal dysfunction. However, other forms of central nervous system alterations have been observed to result from early Pb exposure and alternative explanations for these behavioral changes are also suggested.