Neuroprotective effects of vitamin C and garlic on glycoconjugates changes of cerebellar cortex in lead-exposed rat offspring.

The deteriorating effects of Lead (Pb) on central nervous system (CNS) such as cerebellum has been demonstrated in previous studies. Glycoconjugates with the important role in CNS development may be affected by Pb-exposure. Utilization of antioxidant agents and herbal plants has attracted a great deal of attention on attenuating neurotoxicants-induced damage. Thus, in this study the neuroprotective effects of vitamin C and garlic on content of glycoconjugates of cerebellar cortex in Pb-exposed animals were investigated. Wistar pregnant rats were divided into: control (C), Pb-exposed (Pb) (1500 ppm lead acetate in drinking water), Pb plus vitamin C (Pb + Vit C) (500 mg/kg) intraperitoneally, Pb plus garlic (Pb + G) (1 mL /100 g body weight fresh garlic juice via gavage), Pb plus vitamin C and garlic (Pb + Vit C + G), and sham groups (Sh). Finally, levels of Pb in blood were measured in both rats and offspring on postnatal day 50 (PND50). Also, the cerebellums were removed for measuring Pb-levels and performing lectin histochemistry. Blood and cerebellar Pb-levels were increased in Pb-exposed group compared to control group (P < 0.001), whereas they were decreased significantly in Pb + Vit C, Pb + G, and Pb + Vit C + G groups (P < 0.01). By using MPA, UEA-1, and WGA lectin histochemistry, Pb-exposed group showed weak staining intensity compared to other groups. Besides, significant decrease was observed in the density of lectin-positive neurons of Pb-exposed group compared to the control group (P < 0.001). Moreover, strong staining intensity and high lectin-positive neurons were found in Pb + Vit C, Pb + G and Pb + Vit C + G groups than Pb-exposed group (P < 0.001). The present study revealed that Pb-exposure can result in alteration in the cerebellar glycoconjugates contents and co-administration of vitamin C and garlic could attenuate the adverse effects of Pb. The findings of this study revealed the ameliorating effects of vitamin C and garlic against Pb, suggesting the potential use of vitamin C and garlic as preventive agents in Pb poisoning.

Altered functional activations of prefrontal brain areas during emotional processing of fear in Inuit adolescents exposed to environmental contaminants.

Exposure to mercury, lead and polychlorinated biphenyls (PCBs) have been associated with emotional dysregulation, but their neuronal correlates have yet to be examined. Inuit from Nunavik (Northern Quebec, Canada) face internalizing problems and are among the most exposed individuals to these environmental contaminants in the world. The aim of this study was to examine the link between pre- and postnatal exposure to these contaminants and brain fear-circuitry in Inuit adolescents. Facial expression stimuli were presented to participants (mean age = 18.3 years) in a magnetic resonance imaging (MRI) scanner. Fear conditioning and extinction tasks included neutral faces as the conditioned threat and safety cues and a fearful face paired with a shrieking scream as the unconditioned stimulus. Functional MRI data were gathered at the conditioning phase (n = 71) and at the extinction phase (n = 62). Mercury, lead and PCB 153 concentrations were measured in blood samples at birth (cord blood) and at the time of the adolescent testing to estimate pre- and postnatal exposure, respectively. For each time point, exposures were categorized in tertiles (low, moderate and high exposed groups). Mixed analyses of variance were conducted for each contaminant of interest controlling for sex, age, socioeconomic status, drug/alcohol use, food insecurity and contaminant co-exposure. Results revealed greater differential activation during the conditioning phase in the right orbitofrontal cortex in participants with moderate and high concentrations of cord blood PCB 153 compared to those in the low exposure group. During the extinction phase, the high prenatal mercury exposed group showed a lower differential activation in the right and left anterior cingulate cortex compared to those in the low-exposed group; whereas there was a higher differential activation in right dorsolateral prefrontal cortex in the high postnatal lead exposed group compared to the moderate- and low-exposed groups. Our study is the first to show alterations in the prefrontal brain areas in fear conditioning and extinction tasks in relation to environmental contaminant exposures. The observed brain correlates may advance our understanding of the emotional problems associated with environmental chemical toxicity.

Developmental lead exposure and adult criminal behavior: A 30-year prospective birth cohort study.

Using a variety of research designs and measures of lead absorption, numerous studies link childhood lead exposure to a range of cognitive and behavioral deficits, including low IQ, impulsivity, juvenile delinquency, and criminal behavior in adolescence and early adulthood. In this study, we tested the association between multiple measures of blood lead concentration assessed in childhood with criminal behavior in adulthood and across the life-course. Prospective data from the Cincinnati Lead Study (CLS) included blood lead measures quarterly across the first 78 months of life and the number of times a person was arrested across the life-course (from age 18 to 33 years) and in later adulthood (age 27 to 33 years). Childhood blood lead concentration prospectively predicted variation in adult arrests and arrests over the life-course, indicating lead absorption is implicated in the etiology of crime-especially in geographic areas where environmental sources of lead are more prevalent and concentrated. Efforts to decrease lead exposure in both developed and developing countries should be part of a comprehensive strategy to reduce social dislocation and crime.

Children drinking private well water have higher blood lead than those with city water.

Although the Flint, Michigan, water crisis renewed concerns about lead (Pb) in city drinking water, little attention has been paid to Pb in private wells, which provide drinking water for 13% of the US population. This study evaluates the risk of Pb exposure in children in households relying on private wells. It is based on a curated dataset of blood Pb records from 59,483 North Carolina children matched with household water source information. We analyze the dataset for statistical associations between children's blood Pb and household drinking water source. The analysis shows that children in homes relying on private wells have 25% increased odds (95% CI 6.2 to 48%, P < 0.01) of elevated blood Pb, compared with children in houses served by a community water system that is regulated under the Safe Drinking Water Act. This increased Pb exposure is likely a result of corrosion of household plumbing and well components, because homes relying on private wells rarely treat their water to prevent corrosion. In contrast, corrosion control is required in regulated community water systems. These findings highlight the need for targeted outreach to prevent Pb exposure for the 42.5 million Americans depending on private wells for their drinking water.

Early chronic low-level lead exposure reduced C-C chemokine receptor 7 in hippocampal microglia.

Chronic low-level lead exposure alters cognitive function in young children however the mechanisms mediating these deficits in the brain are not known. Previous studies in our laboratory showed that early lead exposure reduced the number of microglial cells in hippocampus/dentate gyrus of C57BL/6 J mice. In the current study, C-C chemokine receptor 7 (CCR7) and major histocompatibility complex II (MHC II) were examined to investigate whether these neuroimmune factors which are known to trigger cell migration and antigen presentation, were altered by early chronic lead exposure. Thirty-six C57BL/6 J male mice were exposed to 0 ppm (controls, n = 12), 30 ppm (low-dose, n = 12), or 430 ppm (higher-dose, n = 12) of lead acetate via dams' milk from postnatal day (PND) 0 to 28. Flow cytometry was used to quantify cell types and cell surface expression of MHC II and CCR7 in hippocampal and whole brain microglia. Non-parametric independent samples median tests were used to test for statistically significant differences between groups. As compared to controls, CCR7 in hippocampal microglia was decreased in the low-dose group, measured as geometric mean fluorescence intensity (GMFI); in the higher-dose group CCR7+MHC II- hippocampal microglia were decreased. Further analyses revealed that the higher-dose group had decreased percentage of CCR7+MHC II- hippocampal macrophages as compared to controls but increased MHC II levels in CCR7+MHC II+ hippocampal macrophages as compared to controls. It was also noted that lead exposure disrupted the balance of MHC II and/or CCR7 in lead exposed animals. Reduced CCR7 in hippocampal microglia might alter the neuroimmune environment in hippocampi of lead exposed animals. Additional studies are needed to test this possibility.

Fetal exposure to mercury and lead from intrauterine blood transfusions.

BACKGROUND: Mercury (Hg) and lead (Pb) exposure during childhood is associated with irreversible neurodevelopmental effects. Fetal exposure to Hg and Pb from intrauterine blood transfusion (IUBT) has not been reported. METHODS: Fetal exposure was estimated based on transfusion volume and metal concentration in donor packed red blood cell (PRBCs). As biomarkers to quantify prenatal exposure are unknown, Hg and Pb in donor PRBCs were compared to estimated intravenous (IV) RfDs based on gastrointestinal absorption. RESULTS: Three pregnant women received 8 single-donor IUBTs with volumes ranging from 19 to 120 mL/kg. Hg and Pb were present in all donor PRBC units. In all, 1/8 IUBT resulted in Hg dose five times higher than the estimated IV RfD. Median Pb dose in one fetus who received 5 single-donor IUBTs between 20-32 weeks gestation was 3.4 µg/kg (range 0.5-7.9 µg/kg). One donor unit contained 12.9 µg/dL of Pb, resulting in a fetal dose of 7.9 µg/kg, 40 times higher than the estimated IV RfD at 20 weeks gestation. CONCLUSION: This is the first study documenting inadvertent exposure to Hg and Pb from IUBT and quantifying the magnitude of exposure. Screening of donor blood is warranted to prevent toxic effects from Hg and Pb to the developing fetus.

Association between hair lead levels and autism spectrum disorder in children: A systematic review and meta-analysis.

A number of studies measured lead levels in hair from children with autism spectrum disorder (ASD) to detect the relationship between cumulated lead exposure and the development of ASD, but results are inconsistent. We aimed to conduct a systematic review and meta-analysis using the published studies to explore the actual association of hair lead levels with ASD in children. We searched PubMed, Embase, PsycINFO, and Cochrane Library databases (up to December 11, 2018). The random-effects model was applied to summarize effect sizes. Subgroup and meta-regression analyses were performed simultaneously. Twenty eligible studies involving 1787 participants (941 autistic children and 846 healthy subjects) were included. Our results of primary analysis showed that there were no statistically significant differences in the levels of hair lead between children with ASD and healthy individuals (Hedges's g = 0.251; 95% confidence interval: -0.121, 0.623; P = 0.187). We identified 2 sources of between-study heterogeneity: analytical technology and the sample size of patients. Additionally, no publication bias was observed in this meta-analysis. In conclusion, this study does not support the association of hair lead levels with ASD in children, and the involvement of cumulated lead exposure in the occurrence of ASD.

Latent subgroups of cognitive performance in lead- and manganese-exposed Uruguayan children: Examining behavioral signatures.

OBJECTIVES: Lead (Pb) and manganese (Mn) are confirmed neurotoxins but it is unclear to what extent low-level exposure produces a unique behavioral signature. The objective of this study was to investigate latent cognitive profiles among children (6-8 years) from Montevideo, Uruguay co-exposed to these metals. METHOD: Among 345 children, blood Pb and hair Mn were measured using atomic absorption spectroscopy and ICP-MS, respectively. Sixteen measures, reflecting multiple domains of cognitive functioning were gathered: (1) three tests from Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-Extra Dimensional Shift (IED), Spatial Span (SSP) and Stockings of Cambridge (SOC), (2) ten tasks from Woodcock-Muñoz Achievement Battery, Revised (WM): Visual-Motor Integration, Verbal Comprehension (Vocabulary, Synonyms, Antonyms, Analogies), Visual-Auditory Comprehension, Concept Formation, Visual Spatial Thinking, Number Inversion and Spatial Relations, (3) Bender Gestalt task, and (4) Weschler block design task. Scores were modeled using latent profile analysis (LPA). Association between blood Pb and hair Mn on performance profiles was assessed using ordinal regression, controlling for confounders. An interaction between Pb and Mn was tested. RESULTS: Mean ± SD of blood Pb was 4.1 ± 2.1 µg/dL and 35% of children had blood Pb ≥ 5 µg/dL. Median [5%, 95%] hair Mn level was 0.8 [0.3, 4.1] ppb. Three latent cognitive performance profiles were identified: high (n = 46, 13%), average (n = 209, 61%) and low (n = 90, 26%). Each one-unit increase in blood Pb was associated with a 28% greater likelihood of belonging to a poorer-performing profile. The association was non-linear, with the effect of Pb on profile membership strongest at lower levels of exposure. There was no meaningful interaction between Pb and Mn. CONCLUSIONS: A behavioral signature for low-level Pb & Mn exposure was not identified, but the likelihood of membership in low-performing profile was higher at lowest levels of blood Pb. There was no effect measure modification between Pb and Mn. Future research should address how complex environments created by chemical exposures and the social context relate to cognitive performance in young children.

Neurotoxicity of low-level lead exposure: History, mechanisms of action, and behavioral effects in humans and preclinical models.

Lead is a neurotoxin that produces long-term, perhaps irreversible, effects on health and well-being. This article summarizes clinical and preclinical studies that have employed a variety of research techniques to examine the neurotoxic effects of low levels of lead exposure. A historical perspective is presented, followed by an overview of studies that examined behavioral and cognitive outcomes. In addition, a short summary of potential mechanisms of action is provided with a focus on calcium-dependent processes. The current level of concern, or reference level, set by the CDC is 5 µg/dL of lead in blood and a revision to 3.5 µg/dL has been suggested. However, levels of lead below 3 µg/dL have been shown to produce diminished cognitive function and maladaptive behavior in humans and animal models. Because much of the research has focused on higher concentrations of lead, work on low concentrations is needed to better understand the neurobehavioral effects and mechanisms of action of this neurotoxic metal.

Prenatal lead exposure impacts cross-hemispheric and long-range connectivity in the human fetal brain.

Lead represents a highly prevalent metal toxicant with potential to alter human biology in lasting ways. A population segment that is particularly vulnerable to the negative consequences of lead exposure is the human fetus, as exposure events occurring before birth are linked to varied and long-ranging negative health and behavioral outcomes. An area that has yet to be addressed is the potential that lead exposure during pregnancy alters brain development even before an individual is born. Here, we combine prenatal lead exposure information extracted from newborn bloodspots with the human fetal brain functional MRI data to assess whether neural network connectivity differs between lead-exposed and lead-naïve fetuses. We found that neural connectivity patterns differed in lead-exposed and comparison groups such that fetuses that were not exposed demonstrated stronger age-related increases in cross-hemispheric connectivity, while the lead-exposed group demonstrated stronger age-related increases in posterior cingulate cortex (PCC) to lateral prefrontal cortex (PFC) connectivity. These are the first results to demonstrate metal toxicant-related alterations in human fetal neural connectivity. Remarkably, the findings point to alterations in systems that support higher-order cognitive and regulatory functions. Objectives for future work are to replicate these results in larger samples and to test the possibility that these alterations may account for significant variation in future child cognitive and behavioral outcomes.

Elevated lead levels from e-waste exposure are linked to sensory integration difficulties in preschool children.

Exposure to lead is associated with adverse effects on neurodevelopment. However, studies of the effects of lead on sensory integration are few. The purpose of this research is to investigate the effect of lead exposure on child sensory integration by correlating the blood lead levels of children with sensory processing measures. A total of 574 children, from 3 to 6 years of age, 358 from an electronic waste (e-waste) recycling town named Guiyu, and 216 from Haojiang, a nearby town with no e-waste recycling activity, were recruited in this study. The median blood lead level in Guiyu children was 4.88 µg/dL, higher than the 3.47 µg/dL blood lead level in Haojiang children (P < 0.001). 47.2% of Guiyu children had blood lead levels exceeding 5 µg/dL. The median concentration of serum cortisol, an HPA-axis biomarker, in Guiyu children was significantly lower than in Haojiang, and was negatively correlated with blood lead levels. All subscale scores and the total score of the Sensory Processing Measure (Hong Kong Chinese version, SPM-HKC) in Guiyu children were higher than Haojiang children, indicating greater difficulties, especially for touch, body awareness, balance and motion, and total sensory systems. Sensory processing scores were positively correlated with blood lead, except for touch, which was negatively correlated with serum cortisol levels. Simultaneously, all subscale scores and the total SPM-HKC scores for children with high blood lead levels (blood lead > 5 µg/dL) were higher than those in the low blood lead level group (blood lead < 5 µg/dL), especially for hearing, touch, body awareness, balance and motion, and total sensory systems. Our findings suggest that lead exposure in e-waste recycling areas may result in a decrease in serum cortisol levels and an increase in child sensory integration difficulties. Cortisol may be involved in touch-related sensory integration difficulties.

Auditory Training Reverses Lead (Pb)-Toxicity-Induced Changes in Sound-Azimuth Selectivity of Cortical Neurons.

Lead (Pb) causes significant adverse effects on the developing brain, resulting in cognitive and learning disabilities in children. The process by which lead produces these negative changes is largely unknown. The fact that children with these syndromes also show deficits in central auditory processing, however, indicates a speculative but disturbing relationship between lead-exposure, impaired auditory processing, and behavioral dysfunction. Here we studied in rats the changes in cortical spatial tuning impacted by early lead-exposure and their potential restoration to normal by auditory training. We found animals that were exposed to lead early in life displayed significant behavioral impairments compared with naïve controls while conducting the sound-azimuth discrimination task. Lead-exposure also degraded the sound-azimuth selectivity of neurons in the primary auditory cortex. Subsequent sound-azimuth discrimination training, however, restored to nearly normal the lead-degraded cortical azimuth selectivity. This reversal of cortical spatial fidelity was paralleled by changes in cortical expression of certain excitatory and inhibitory neurotransmitter receptor subunits. These results in a rodent model demonstrate the persisting neurotoxic effects of early lead-exposure on behavioral and cortical neuronal processing of spatial information of sound. They also indicate that attention-demanding auditory training may remediate lead-induced cortical neurological deficits even after these deficits have occurred.

Early chronic exposure to low-level lead alters total hippocampal microglia in pre-adolescent mice.

Developmental lead (Pb) exposure alters brain function through mechanisms that are not yet understood. A previous study showed that early lead exposure reduced microglia number in the dentate gyrus region of the hippocampus. Given the critical role of microglia in brain development, it is important to determine whether these differences are unique to the dentate gyrus, or occur throughout the hippocampus. Unbiased stereology was used to quantify microglia mean cell body number in total hippocampus, and compare the proportion of microglia in the ventral vs. dorsal regions. Total hippocampal volume was also measured and compared. The study included brain tissue from 30 pre-adolescent C57BL/6 J mice, exposed to 30 ppm Pb acetate (n = 10, mean BLL 3.4 µg/dL at sacrifice), 330 ppm Pb acetate (n = 10, mean BLL 14.1 µg/dL at sacrifice), or 0 ppm Pb acetate (n = 10, negative controls). In lead exposed animals, microglia mean cell body number was reduced in total hippocampus; total hippocampal volume was reduced. Importantly, effects in low- and high-dose exposure groups did not differ. Contrary to study hypotheses, the distribution of hippocampal microglia in the ventral vs. dorsal hippocampal regions did not differ. Overall, lowest and higher levels of lead exposure during development had strikingly similar disruptive effects in the neuroimmune system. Studies are needed to determine the immune and other mechanisms responsible for these effects. Future studies would benefit from larger samples to determine whether in fact there is a group by sex interaction driving the effects of early lead exposure on microglia.

Reduced regional volumes associated with total psychopathy scores in an adult population with childhood lead exposure.

Childhood lead exposure has been correlated to acts of delinquency and criminal behavior; however, little research has been conducted to examine its potential long term influence on behavioral factors such as personality, specifically psychopathic personality. Neuroimaging studies have demonstrated that the effects of childhood lead exposure persist into adulthood, with structural abnormalities found in gray and white matter regions involved in behavioral decision making. The current study examined whether measurements of adult psychopathy were associated with neuroanatomical differences in structural brain volumes for a longitudinal cohort with measured childhood lead exposure. We hypothesized that increased total psychopathy scores and increased blood lead concentration at 78 months of age (PbB78) would be inversely associated with volumetric measures of gray and white matter brain structures responsible for executive and emotional processing. Analyses did not display a direct effect between total psychopathy score and gray matter volume; however, reduced white matter volume in the cerebellum and brain stem in relation to increased total psychopathy scores was observed. An interaction between sex and total psychopathy score was also detected. Females displayed increased gray matter volume in the frontal, temporal, and parietal lobes associated with increased total psychopathy score, but did not display any white matter volume differences. Males primarily displayed reductions in frontal gray and white matter brain volume in relation to increased total psychopathy scores. Additionally, reduced gray and white matter volume was associated with increased blood lead levels in the frontal lobes; reduced white matter volume was also observed in the parietal and temporal lobes. Females demonstrated gray and white matter volume loss associated with increased PbB78 values in the right temporal lobe, as well as reduced gray matter volume in the frontal lobe. Males displayed reduced white matter volumes associated with increased PbB78 values in the frontal, temporal, and parietal lobes. Comparison of the two primary models revealed a volumetric decrease in the white matter of the left prefrontal cortex associated with increased total psychopathy scores and increased blood lead concentration in males. The results of this study suggested that increased psychopathy scores in this cohort may be attributable to the neuroanatomical abnormalities observed and that childhood lead exposure may be influential to these outcomes.

Lead in a case of encephalopathy.

A 2-year-old boy with a history of pica was admitted with vomiting and treated overnight for viral tonsillitis. A week later, he presented with a prolonged afebrile seizure and required intubation and ventilation. Antibiotics and acyclovir were started. Despite extensive investigations including MRI head, no cause was identified. Four days later, he deteriorated with signs of raised intracranial pressure. On day 5, blood lead concentration in the sample collected at admission was reported as grossly elevated, consistent with a diagnosis of severe lead poisoning from ingesting lead-containing paint at the family home. Chelation therapy was started but, unfortunately, he did not make a neurological recovery, and care was withdrawn. A serious case review identified a lack of awareness of lead poisoning and its relation to pica as a root cause. We report this case to share our experience and the importance of considering lead poisoning in children with pica.

From the Cover: 7,8-Dihydroxyflavone Rescues Lead-Induced Impairment of Vesicular Release: A Novel Therapeutic Approach for Lead Intoxicated Children.

Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits. In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling. The objective of this study was to determine if activation of TrkB, the cognate receptor for BDNF, would rescue Pb2+-induced impairments of vesicular release. Rats were chronically exposed to Pb2+ prenatally and postnatally until 50 days of age. This chronic Pb2+ exposure paradigm enhanced paired-pulse facilitation of synaptic potentials in Schaffer collateral-CA1 synapses in the hippocampus, a phenomenon indicative of reduced vesicular release probability. Decreased vesicular release probability was confirmed by both mean-variance analysis and direct 2-photon imaging of vesicular release from hippocampal slices of rats exposed to Pb2+in vivo. We also found a Pb2+-induced impairment of calcium influx in Schaffer collateral-CA1 synaptic terminals. Intraperitoneal injections of Pb2+ rats with the TrkB receptor agonist 7,8-dihydroxyflavone (5 mg/kg) for 14-15 days starting at postnatal day 35, reversed all Pb2+-induced impairments of presynaptic transmitter release at Schaffer collateral-CA1 synapses. This study demonstrates for the first time that in vivo pharmacological activation of TrkB receptors by small molecules such as 7,8-dihydroxyflavone can reverse long-term effects of chronic Pb2+ exposure on presynaptic terminals, pointing to TrkB receptor activation as a promising therapeutic intervention in Pb2+-intoxicated children.

The effects of lead on GABAergic interneurons in rodents.

Lead is a heavy metal that affects various systems and organs in the body, especially the nervous system. In this study, the in vivo and in vitro effects of lead on neurons were analyzed. We divided mouse pups into three groups based on the concentration of lead exposure: the control group, the low-dose group, and the high-dose group. Changes in behavior (measured by an open-field test and a tail suspension test), blood lead levels (measured by atomic absorption spectrophotometry), the number of GABAergic interneurons (measured by immunohistochemistry), gene expression (measured by qRT-PCR), and DNA methylation (measured by pyrosequencing) were determined in the three groups. The lead-exposed pups showed significantly higher blood lead levels ( p < 0.001). Lead exposure caused hyperactivity and reduced the body weight of the exposed mice compared with that of the controls. The lead-exposed groups showed significantly lower numbers of parvalbumin and neuropeptide Y interneurons and lower expression levels of distal-less homeobox ( Dlx) 1, 2, 5, and 6 genes in the cerebral cortex. To further clarify the mechanism of Dlx gene downregulation, we selected the GE6 cell line, which can differentiate into various subtypes of GABAergic interneurons, for in vitro experiments. We found that high levels of lead also inhibited the expression of Dlx 1/ 2/ 5/ 6 in vitro, but DNA methylation levels were not changed in the GE6 cell line. Furthermore, lead exposure significantly decreased the expression of Olig1 and Ki67 and increased that of Tubb3 in vitro. The present study revealed that lead exposure can alter behaviors, reduce the number of GABAergic interneurons, and change the expression of some important genes in neuronal cells.