Effects of lead, mercury, aluminium and manganese co-exposure on the serum BDNF concentration of pre-school children in Taizhou, China
Introduction
Chronic exposure to toxic metals, such as lead (Pb), mercury (Hg), aluminium (Al) and manganese (Mn), has raised worldwide concern because of their deleterious effects (Counter and Buchanan, 2004). The main sources of these toxic metals are contaminated dust, food and water (Luo et al., 2017). Exposure to these toxic heavy metals has been implicated in renal disorders, bone loss, cardiovascular diseases and neurodevelopmental disorders (Kim et al., 2009, Zhang et al., 2012, Chen et al., 2014, Wang et al., 2018). Due to the sensitivity of the developing nervous system, children are more susceptible to environmental toxic exposure. Childhood Pb exposure is associated with decreases in intellectual function and brain volume, and with a disturbed brain cholesterol metabolism (Cecil et al., 2008, Mazumdar et al., 2011, Zhou et al., 2018). Early life Hg exposure is negatively associated with psychomotor development and decreased behavioural abilities (Gao et al., 2007, Llop et al., 2012). Al accumulation in the brain can inhibit neurodevelopment, induce neuroinflammation and contribute to the pathogenesis of Alzheimers’s disease (AD) (Wang et al., 2013). Mn, as an essential mineral nutrient, plays a crucial role in various metalloenzymes, and excessive exposure to Mn can also be related to neurotoxic effects, including declined cognition, motor function and behaviour disorders in children (Aschner and Aschner, 1991, Wasserman et al., 2006, Khan et al., 2011). Nevertheless, simultaneous chronic exposure to these toxic metals is more environmentally relevant in many circumstances, and economically disadvantaged children are often exposed to various combinations of toxic metals (Pan et al., 2018). Animal experiments have suggested that metal arsenic (As), cadmium (Cd) and Pb co-exposure induces additive toxic effects in the brain in developing rats (Rai et al., 2010). Epidemiological studies have also shown that toxic metals co-exposure might have more severe effects on the neurodevelopment, intelligence and psychomotor development of children than exposure to each metal alone (Wright et al., 2006, Kim et al., 2013). However, there is little information on the possible interaction effects of simultaneous exposure to Pb, Hg, Al, and Mn in pre-school children.
Many studies have investigated the neurotoxic mechanisms of toxic metal exposure, such as increased oxidative stress, disrupted calcium metabolism and impaired dopamine neurotransmission (Zhang et al., 2012), but the toxicology of metal exposure on neurodevelopment remains to be clarified. Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in nervous system development, synaptic plasticity and cognition function (Levine et al., 1998, Erickson et al., 2012, Keshavarz et al., 2016). The expression of BDNF is modulated by N-methyl-D-aspartate (NMDA) receptors via the Ca2+ signalling pathway (Levine et al., 1998). Previous studies have reported that the serum BDNF concentrations are positively correlated with the brain BDNF levels and the Montreal Cognitive Assessment (MoCA) scores in Mn-exposed workers. (Klein et al., 2011, Zou et al., 2014). Decreased cord serum BDNF levels are positively associated with declined infants’ social score, which is a specific domain of the developmental quotient (DQ) (Wang et al., 2016). Meanwhile, a deficiency of the serum BDNF concentration is associated with a decreased hippocampus volume and reduced dendritic complexity (Erickson et al., 2010, von Bohlen und Halbach, 2010). Many epidemiological studies have associated exposure to toxic metals with adverse effects on the nervous system in children (Gao et al., 2007, Zhou et al., 2018). Meanwhile, many studies have demonstrated that metal exposure significantly decreased the serum BDNF levels in rats and populations (Stansfield et al., 2012, Yu et al., 2016). However, to the best of our knowledge, the relationship between Pb, Hg, Al and Mn co-exposure and serum BDNF levels in pre-school children has not been investigated.
Gender-related differences in susceptibility to metal exposure have been investigated in many studies, but the results remain controversial. Some experimental studies have demonstrated that Pb-induced neurodevelopmental impairment, which include impairments in motor responses and spatial learning, is more prevalent in males than in females (Yang et al., 2003, Leasure et al., 2008). Our previous study also found a significant inverse association between the cord blood Pb levels and children’s head circumference only in males (Wang et al., 2017). In addition, some studies found that prenatal Hg exposure impairs learning ability and working memory in females (Goulet et al., 2003, Yoshida et al., 2005), whereas another study found that prenatal Hg exposure decreased learning and behaviour activities in males (Onishchenko et al., 2007). We also reported that increased prenatal Hg exposure is associated with decreased behavioural abilities in males but not in females (Gao et al., 2007). A higher susceptibility to Mn has been observed in males in some animal studies (Madison et al., 2011). However, in Riojas-Rodriguez et al. found significant negative effects of Mn in girls (Riojas-Rodriguez et al., 2010). Nevertheless, limited studies have investigated the effects of toxic metal co-exposure on neurodevelopment, involving serum BDNF expression in pre-school children stratified by gender.
Therefore, the aim of this study was to assess the association between blood Pb, Hg, Al and Mn levels and serum BDNF concentrations in pre-school children in Taizhou City, Zhejiang province, China. The objectives of this study were to (1) determine the blood levels of Pb, Hg, Al and Mn in pre-school children in Taizhou City; (2) explore the association between Pb, Hg, Al and Mn levels and serum BDNF concentration stratified by gender; and (3) investigate the effects of metal co-exposure on serum BDNF concentrations stratified by gender.
Section snippets
Study subjects and recruitment
This study was conducted in Taizhou City, Zhejiang province, China, from April 2013 to November 2013. This study was approved by the Ethics Committee of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Written informed consent was obtained from the children’s parents. In our study, we sent out 600 invitations to the parents. Children were excluded if they diagnosed had heavy metal exposure history (n = 4). Meanwhile, the data in questionnaires were incomplete
Results
The GMs of the blood Pb, Hg, Al, Mn levels and serum BDNF concentrations of the study participants by age, sex, maternal education, paternal education, household monthly salary, fresh-fish consumption frequency and saltwater-fish consumption frequency are presented in Table 1. Overall, a total of 561 children, including 302 boys and 259 girls, were recruited, and the GMs of the blood Pb, Hg, Al and Mn levels of all the participants were 67.18 μg/L, 1.01 μg/L, 52.03 μg/L and 18.26 μg/L,
Discussion
This study is the first time to report the levels of Pb, Hg, Al and Mn in the blood of pre-school children in Taizhou City, Zhejiang province, China. Taizhou is a coastal city, there were many battery production, metal recycling and production of Pb containing chemicals in the past. In addition, there were numerous small family businesses that use Pb-containing products in these years. Therefore, children’s exposure to toxic metal is still very common. In our study, we evaluated the metal
Conflicts of interest
None.
Acknowledgments
This work was supported by the National Basic Research Program of China (973 Program, 2012CB525001) and the National Natural Science Foundation of China (Grant No. 81472993).
References (59)
- et al.
Brain-derived neutrophic factor in adolescents smoking waterpipe: the Irbid TRY
Int. J. Dev. Neurosci. : the Off. J. Int. Soc. Dev. Neurosci.
(2018) - et al.
Manganese neurotoxicity: cellular effects and blood-brain barrier transport
Neurosci. Biobehav. Rev.
(1991) - et al.
Relationship between blood manganese levels and children’s attention, cognition, behavior, and academic performance--a nationwide cross-sectional study
Environ. Res.
(2013) - et al.
Effects of lead and cadmium co-exposure on bone mineral density in a Chinese population
Bone
(2014) - et al.
Mercury exposure in children: a review
Toxicol. Appl. Pharmacol.
(2004) - et al.
Prenatal exposure to mercury and neurobehavioral development of neonates in Zhoushan City, China
Environ. Res.
(2007) - et al.
Blood mercury concentration, fish consumption and anthropometry in Chinese children: a national study
Environ. Int.
(2018) - et al.
Perinatal exposure to lead (Pb) induces ultrastructural and molecular alterations in synapses of rat offspring
Toxicology
(2016) - et al.
Neurobehavioral changes in mice chronically exposed to methylmercury during fetal and early postnatal development
Neurotoxicol. Teratol.
(2003) - et al.
Levels of prenatal mercury exposure and their relationships to neonatal anthropometry in Wujiang City, China
Environ. Pollut.
(2013)
Blood cadmium, mercury, and lead in children: an international comparison of cities in six European countries, and China, Ecuador, and Morocco
Environ. Int.
Gender specific differences in neurodevelopmental effects of prenatal exposure to very low-lead levels: the prospective cohort study in three-year olds
Early Hum. Dev.
Prenatal lead and cadmium co-exposure and infant neurodevelopment at 6 months of age: the Mothers and Children’s Environmental Health (MOCEH) study
Neurotoxicology
Co-exposure to environmental lead and manganese affects the intelligence of school-aged children
Neurotoxicology
The national trend of blood lead levels among Chinese children aged 0-18 years old, 1990-2012
Environ. Int.
Gender and manganese exposure interactions on mouse striatal neuron morphology
Neurotoxicology
Effects of lead, cadmium, arsenic, and mercury co-exposure on children’s intelligence quotient in an industrialized area of southern China
Environ. Pollut.
Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data
Brain Res. Bull.
Sex differences in the effects of prenatal lead exposure on birth outcomes
Environ. Pollut.
Aluminum(III) interferes with the structure and the activity of the peptidyl-prolyl cis-trans isomerase (Pin1): a new mechanism contributing to the pathogenesis of Alzheimer’s disease and cancers?
J. Inorg. Biochem.
Effects of prenatal exposure to cadmium on neurodevelopment of infants in Shandong, China
Environ. Pollut.
Al and Fe levels in mixed saliva of children related to elution behavior from teeth and restorations
J. Trace Elem. Med. Biol.: organ of the Soc. Miner. Trace Elements (GMS)
Neuropsychological correlates of hair arsenic, manganese, and cadmium levels in school-age children residing near a hazardous waste site
Neurotoxicology
Lead exposure through gestation-only caused long-term learning/memory deficits in young adult offspring
Exp. Neurol.
Neurobehavioral changes in metallothionein-null mice prenatally exposed to mercury vapor
Toxicol. Lett.
The role of cord blood BDNF in infant cognitive impairment induced by low-level prenatal manganese exposure: LW birth cohort, China
Chemosphere
Serum neurotrophins--a study on the time course and influencing factors in a large old age sample
Neurobiol. Aging
Environmental lead exposure among preschool children in Shanghai, China: blood lead levels and risk factors
PloS One
Decreased brain volume in adults with childhood lead exposure
PLoS Med.
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These authors contributed equally to this work.