Elevated lead levels in relation to low serum neuropeptide Y and adverse behavioral effects in preschool children with e-waste exposure
Introduction
With the rapid development of electronic industry, the innovation of global electronic products and the acceleration of electronic equipment or products upgrading in recent years, electronic waste (e-waste) have become the fastest growing garbage in the world (Zeng et al., 2020). E-waste refers to discarded electrical and electronic equipment after the end of its service life, whose abandoned components have contained potentially harmful contaminants such as heavy metals and persistent organic pollutants (Zeng et al., 2019). It was estimated that China generated the highest e-waste quantity (approximately 20% of global e-waste) both in Asia and in the world, and only 15% of e-waste has been documented to be collected and properly recycled (Zhang et al., 2012; Song and Li, 2014; Heacock et al., 2016; Zeng et al., 2016a, Zeng et al., 2016b; Priyadharsini and Singh, 2019). E-waste can be stored in a variety of environmental media including air, dust, soil, water, and sediment for a long time, which will inevitably cause environmental media pollution and pose a threat to the health of local residents (Robinson, 2009). Guiyu, a town located in southeast of China, is well known e-waste destination with informal and primitive recycling style in term of home-based workshops (Wu et al., 2010). Although a centralized industrial park has been recently established to recycle e-waste, the operation mode is rent workshop to individual merchants. Therefore, the improper and unsafe disposal activity is still exist companying with the process of e-waste collecting and recycling due to economic benefits in Guiyu (Alassali et al., 2020). It cannot be ignored that e-waste exposure and subsequently environmental pollutants have serious impaired human health.
Among the various environmental contaminants, especially heavy metals, lead (Pb) has attracted widespread attention by researchers for its characteristics of major and typical with higher exposure level compared with other areas over the world (Zeng et al., 2020; Zhang et al., 2020). It is well known that Pb is a non-degradable hazardous substance with cumulative toxicity. In addition, there is no safe exposure level to Pb, even at a very low level. Pb can enter the bloodstream quickly and easily through the inhalation, ingestion and skin adsorption in the form of fine particles, aerosols and their vapors (Nehru et al., 2001; Zeng et al., 2016a, Zeng et al., 2016b). Previous studies showed that Pb has been the most typical heavy metal in e-waste with high content in Guiyu (Wong et al., 2007; Xu et al., 2015; Zeng et al., 2020). In particular, Pb in the road dust of Guiyu is 330 and 106 times higher than non-e-waste sites located 8 and 30 km away, respectively (Leung et al., 2008). Preschool children are more likely to contact dust Pb because that they have special physical and behavioral characteristics when compared with adults. For instances, preschool children with lower height closer to the ground are more likely to inhale more dust Pb; preschool children with higher frequency of hand-to-mouth activity during playing outdoor are more likely to ingest more environmental medium Pb (Heacock et al., 2016; Zeng et al., 2020). Our previous studies demonstrated that preschool children living in Guiyu have significantly higher blood Pb levels than those from the reference areas (Huo et al., 2007; Liu et al., 2011, 2018; Xu et al., 2015; Zeng et al., 2016, 2017; Zeng et al., 2017a, Zeng et al., 2017b; Chen et al., 2019; Hou et al., 2020; Zhang et al., 2020). Percentages of preschool children with blood Pb levels ≥5 μg/dL (the recommended limit) were higher in Guiyu than those in the reference areas (Zheng et al., 2019; Hou et al., 2020; Zhang et al., 2020). This indicates that environmental and blood Pb exposure is still very serious in Guiyu and cause a considerable health burden to children and their families.
It is well known that children are at great risk of Pb poisoning which is not only impair peripheral nervous systems, but also damage the central nervous system (CNS) and the developing brain (Sanders et al., 2009). The key mechanism of Pb affecting the CNS is that it can impair and subsequently pass through the blood-brain barrier (BBB) partly for its ability to substitute for various polyvalent cations such as calcium (Ca2+) and zinc (Zn2+) ions (Garza et al., 2006; Wu et al., 2020). The biological process of competitive substitution of Pb2+ for Ca2+ or Zn2+ significantly impact metal transport, ionic conduction, signal transduction, energy metabolism, and genetic regulation. The flow and interaction of ions, molecules, and cells between blood and brain is precisely regulated by the BBB that is a structural and functional interface closely dominating the extracellular environment of brain (Friedman and Kaufer, 2015; Profaci et al., 2020). The impaired or dysfunction of blood brain barrier will certainly contribute to cognitive dysfunction, altered behavior, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (Zenaro et al., 2017; Nation et al., 2019; Israelov et al., 2020). In addition, Pb exposure can cause acute or chronic symptoms such as mental retardation, learning disabilities, emotional problems, and behavioral disorders (Canfield et al., 2003; Liu et al., 2014a,b; Taylor et al., 2017; Freire et al., 2018). For an instance, elevated blood Pb was correlated with decrease in IQ and cognitive function even blood Pb level <5 μg/dL (Koller et al., 2004; Huang et al., 2012; Gump et al., 2017). Persistent behavioral problems have been shown to have a negative impact on children’s intellectual, psychosocial, and academic development (Jansen et al., 2007). However, the effects of Pb outside CNS remain unclear. The neurotransmitters such as neuropeptide Y, substance P and dopamine are broadly expressed in the central and peripheral nervous system during childhood, and may function as a link between Pb and CNS, and further play a mediate role in Pb triggering behavioral problem (Hansel et al., 2001).
Neurotransmitters such as Neuropeptide Y (NPY) and Substance P (SP) involve in handling the emotion-eliciting information in the limbic system (Dalgleish, 2004). NPY is an important anxiolytic endogenous peptide being modulated by chronic stress, which is considered to play a very important role in emotion and stress coping (Heilig and Thorsell, 2002; Sah and Geracioti, 2013; Enman et al., 2015). In addition, it can induce regeneration of hippocampal neurons and participate in changes of synaptic plasticity. What is more, NPY neurons have been shown to interact with behavioral brain pathways and dopaminergic reward in the amygdala and nucleus accumbens, respectively (Dalgleish, 2004; Heilig, 2004; Morales-Medina et al., 2010). Substance P is highly expressed in hypothalamus, amygdaloid nucleus, and the periaqueductal gray, regulating emotion (Datar et al., 2004; Herpfer et al., 2007; Lorente et al., 2019). Elevated substance P levels are associated with increased inner tension and anxiety (Ebner and Singewald, 2006; Herpfer et al., 2007; Iftikhar et al., 2020). Previous studies demonstrated that the release of NPY and substance P have been proven to be activity-dependent, which can be modulated by N-methyl-d-aspartate (NMDA) receptor through the Ca2+ signaling pathway. Dopamine plays a crucial role in regulating behavior and emotions, and dopamine alteration lead to abnormal behaviors such as impulsivity and hyperactivity (Nieoullon and Coquerel, 2003; Strafella, 2019). Dysregulation of dopamine neurotransmission in dorsal striatal dopamine system is associated with the processing of negative human emotions (Badgaiyan, 2010; Chang et al., 2019). Persistent and developmental Pb exposure induces depressive behavior both in rats and children (Sciarillo et al., 1992; de Souza et al., 2005; Liu et al., 2014a,b).
Pb can enter the well-protected brain through damaging BBB for competing and substituting calcium and its roles in communication among neurons. In general, calcium enters the activated neuron and triggers the release of neurotransmitters such as neuropeptide Y, substance P and dopamine. Neurotransmitters participate in cascade reaction carrying neuronal signaling from the first neuro to the next nearby neuron until the signal reaching its target. Less Ca enter the neuron when competed with Pb, and subsequently weaker signal release from neurotransmitter to neuron. In addition, Pb also cause inappropriate neurotransmitter release in resting/non-activated neurons and subsequently abnormal signals to later neurons. The above-mention process will lead to behavioral alterations. Long term Pb exposure increased immune-reactivities of anti-serotonin (anti-5HT) and tyrosine hydroxylase (anti-TH), and induced behavioral changes such as hyperactivity and anxiety in meriones (Bouyatas et al., 2019). Exposures to Pb are associated with increased repetitive behavior in mice, which linked with changed neurotransmission of dopamine (Chang et al., 2014). There are some studies investigating the effects of Pb on behavioral problems in animals and humans (Rice et al., 1996; Moreira et al., 2001; Bellinger et al., 2008; Liu et al., 2014a,b). Our previous study demonstrated that children exposed to Pb in an e-waste recycling area more like to have a higher blood Pb level and a lower cognitive and language scores when compared with the reference group (Liu et al., 2015). However, study on Pb-linked behavioral toxicity is inadequate in preschoolers from e-waste dismantling areas. Therefore, this study was designed to assess the adverse effects of Pb on behavioral health in e-waste-exposed preschool children.
Section snippets
Study population
A total of 213 children (3–7 years old) from Guiyu (n = 112, the e-waste-exposed area) and Haojiang (n = 101, the reference area) which is located 31.6 km to the east of Guiyu. Both areas were similar in population, local customs and socioeconomic status. The big difference between the two areas is that e-waste pollution occurs only in Guiyu but not in Haojiang (Zeng et al., 2017a, Zeng et al., 2017b). Participants were recruited during the period of October to December 2017. The venous blood
Demographic characteristics of the study population
The demographic characteristics of the 213 participants are shown in Table 1. The average age of the children in the e-waste exposed group and the reference group was 4.73 ± 0.77 years and 4.87 ± 0.86 years, respectively. The average of age showed no significant difference between the two groups (p > 0.05). The blood Pb concentration of exposed children was 5.19 μg/dL, which was almost 1.5-times higher than the 3.42 μg/dL for reference children (p < 0.001). Furthermore, the percentage of blood
Discussion
The present study explored the correlation between Pb exposure and the behavioral health in children aged 3- to 7- years old in an e-waste recycling area. The changes of three serum biomarkers of the behavioral disturbance were measured and the behavioral health status was evaluated using the SDQ in children from both e-waste and reference groups. Our results show that the average blood Pb level of children in Guiyu is 5.19 μg/dL, and about 54.5% Guiyu children with blood Pb level exceed
Conclusion
In summary, the present research finds that the prevalence of behavioral difficulties in children from Guiyu is higher (48.2%) than those from the reference area. The results of this study show that Pb exposure in e-waste recycling regions lead to a decrease in serum NPY levels, an increase in substance P concentration, and a higher risk for behavioral difficulties. Additionally, NPY and substance P might be associated with the behavioral health of children. Taken together, strategies to
Credit author statement
Xiang Zeng: Writing - original draft, Conceptualization. Cheng Xu: Writing - original draft. Xijin Xu: Conceptualization, Supervision, Writing - review & editing, Validation. Yu Zhang: Writing - review & editing. Yu Huang: Writing - review & editing. Xia Huo: Conceptualization, Supervision, Writing - review & editing, Validation, Funding acquisition.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments. This study protocol was approved by the Human Ethics Committee of Shantou University Medical College, China. All parents and guardians of children agreed to enroll, and offered written informed-consent for participation.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
First of all, we would like to extend my sincere gratitude to all the recruited participator in this scheme. We also acknowledge Dr. Stanley Lin for his instructive suggestions and English language editing. This work was supported by the National Natural Science Foundation of China (21876065).
References (107)
Modulation of hippocampal long-term potentiation by the amygdala: a synaptic mechanism linking emotion and memory
Jpn. J. Pharmacol.
(2001)- et al.
Towards a high quality recycling of plastics from waste electrical and electronic equipment through separation of contaminated fractions
J. Hazard Mater.
(2020) - et al.
Neurotoxicity of lead. Hypothetical molecular mechanisms of synaptic function disorders
Neurol. Neurochir. Pol.
(2012) - et al.
Hippocampal NMDA receptors and anxiety: at the interface between cognition and emotion
Eur. J. Pharmacol.
(2010) - et al.
Effects of substance P and Sar-Met-SP, a NK1 agonist, in distinct amygdaloid nuclei on anxiety-like behavior in rats
Neurosci. Lett.
(2014) - et al.
Reduced regional volumes associated with total psychopathy scores in an adult population with childhood lead exposure
Neurotoxicology
(2018) - et al.
Neurobehavioral effects of acute and chronic lead exposure in a desert rodent Meriones shawi: involvement of serotonin and dopamine
J. Chem. Neuroanat.
(2019) - et al.
The influence of age of lead exposure on adult gray matter volume
Neurotoxicology
(2010) - et al.
Blood lead and cadmium levels associated with hematological and hepatic functions in patients from an e-waste-polluted area
Chemosphere
(2019) - et al.
Targeting the neuropeptide Y system in stress-related psychiatric disorders
Neurobiol Stress
(2015)
Prenatal co-exposure to neurotoxic metals and neurodevelopment in preschool children: the Environment and Childhood (INMA) Project
Sci. Total Environ.
Blood-brain barrier in health and disease
Semin. Cell Dev. Biol.
Background lead and mercury exposures: psychological and behavioral problems in children
Environ. Res.
Exposure to airborne metals and particulate matter and risk for youth adjudicated for criminal activity
Environ. Res.
The NPY system in stress, anxiety and depression
Neuropeptides
Elevated levels of lead exposure and impact on the anti-inflammatory ability of oral sialic acids among preschool children in e-waste areas
Sci. Total Environ.
Childhood blood lead levels and intellectual development after ban of leaded gasoline in Taiwan: a 9-year prospective study
Environ. Int.
Substance P: a neuropeptide involved in the psychopathology of anxiety disorders
Neuropeptides
The involvement of substance P in the induction of aggressive behavior
Peptides
Nutritional status and diet as predictors of children’s lead concentrations in blood and urine
Environ. Int.
Association between lead exposure from electronic waste recycling and child temperament alterations
Neurotoxicology
Neurotoxicity and biomarkers of lead exposure: a review
Chin. Med. Sci. J.
Thyroid disruption and reduced mental development in children from an informal e-waste recycling area: a mediation analysis
Chemosphere
S100β in heavy metal-related child attention-deficit hyperactivity disorder in an informal e-waste recycling area
Neurotoxicology
Persistently high serum substance P levels and early mortality in patients with severe traumatic brain injury
World Neurosurg
Synaptic plasticity in depression: molecular, cellular and functional correlates
Prog. Neuro-Psychopharmacol. Biol. Psychiatry
Scale properties of the Japanese version of the Strengths and Difficulties Questionnaire (SDQ): a study of infant and school children in community samples
Brain Dev.
Spatial-temporal association of soil Pb and children’s blood Pb in the Detroit Tri-County Area of Michigan (USA)
Environ. Res.
Developmental lead exposure: behavioral alterations in the short and long term
Neurotoxicol. Teratol.
A possible role of neuropeptide Y in depression and stress
Brain Res.
The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY-induced antidepressant-like activity in the mouse forced swimming test
Neuropsychopharmacology
E-waste: an assessment of global production and environmental impacts
Sci. Total Environ.
Plasma levels of neuropeptides and metabolic hormones, and sleepiness in obstructive sleep apnea
Respir. Med.
Prenatal exposure to environmental contaminants and behavioural problems at age 7-8years
Environ. Int.
A systematic review of the human body burden of e-waste exposure in China
Environ. Int.
Psychotic-like experiences, trauma and related risk factors among "left-behind" children in China
Schizophr. Res.
Data relating to prenatal lead exposure and child IQ at 4 and 8 years old in the Avon Longitudinal Study of Parents and Children
Neurotoxicology
Evidence of excessive releases of metals from primitive e-waste processing in Guiyu, China
Environ. Pollut.
Environmental lead exposure aggravates the progression of Alzheimer’s disease in mice by targeting on blood brain barrier
Toxicol. Lett.
Association of polycyclic aromatic hydrocarbons (PAHs) and lead co-exposure with child physical growth and development in an e-waste recycling town
Chemosphere
The blood-brain barrier in Alzheimer’s disease
Neurobiol. Dis.
E-waste lead exposure and children’s health in China
Sci. Total Environ.
Children with health impairments by heavy metals in an e-waste recycling area
Chemosphere
Decreased lung function with mediation of blood parameters linked to e-waste lead and cadmium exposure in preschool children
Environ. Pollut.
Dopamine is released in the striatum during human emotional processing
Neuroreport
Association of childhood blood lead levels with criminal offending
JAMA Pediatr
Neurological and behavioral consequences of childhood lead exposure
PLoS Med.
CDC updates guidelines for children’s lead exposure
Environ. Health Perspect.
The normative development of child and adolescent problem behavior
J. Abnorm. Psychol.
Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter
N. Engl. J. Med.
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These authors contributed equally to this work.