Estimation of autistic children by metallomics analysis

La Belle Vie Research Laboratory, 8-4 Nihonbashi-Tomizawacho , Chuo-ku, Tokyo, Japan.
Scientific Reports (Impact Factor: 5.58). 08/2013; 3(1199):1199. DOI: 10.1038/srep01199
Source: PubMed


Clarification of the pathogenesis and treatment of autism spectrum disorders is one of the challenges today. In this study, we examine scalp hair concentrations of 26 trace elements for 1,967 children with autistic disorders (1,553 males and 414 females). Five-hundred and eighty-four (29.7%), 347 (17.6%) and 114 (5.8%) subjects was found deficient in zinc, magnesium and calcium, respectively, and 2.0% or less in the other essential metals. The incidence rate of mineral deficiency was highly observed in infants aged 0-3 year-old. In contrast, 339 (17.2%), 168 (8.5%) and 94 (4.8%) individuals was found suffering from high burden of aluminium, cadmium and lead, and 2.8% or less from mercury and arsenic burden. These findings suggest that infantile zinc- and magnesium-deficiency and/or toxic metal burdens may epigenetically play principal roles as environmental factors in autistic disorders and that metallomics approach may lead to early screening and prevention of the neurodevelopment disorders.

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Available from: Hiroshi Yasuda, Sep 18, 2014
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    • "This is based on evidence suggesting the plausibility of a role for mercury in the etiology of autism [29] [30], and mercury in maternal peripheral and cord blood has been shown to affect fetal epigenetic status [31]. A handful of reports also points out to other heavy metals neurotoxicity and epigenetic mechanism [32] [33]. The experiments presented in this paper were designed to identify abnormal neurobehavioral phenotypes resulting from in utero exposure to several identified environmental pollutants. "
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    ABSTRACT: We tested the hypothesis that in utero exposure to heavy metals increases autism-like behavioral phenotypes in adult animals and induces epigenetic changes in genes that have roles in the etiology of autism. Mouse dams were treated with cadmium, lead, arsenate, manganese, and mercury via drinking water from gestational days (E) 1–10. Valproic acid (VPA) injected intraperitoneally once on (E) 8.5 served as a positive control. Young male offspring were tested for behavioral deficits using four standardized behavioral assays. In this study, in utero exposure to heavy metals resulted in multiple behavioral abnormalities that persisted into adulthood. VPA and manganese induced changes in perseverative/impulsive behavior and social dominance behavior, arsenic caused changes only in perseverative/impulsive behavior, and lead induced abnormalities in social interaction in comparison to the control animals. Brain samples from Mn, Pb, and VPA treated and control animals were evaluated for changes in CpG island methylation in promoter regions and associated changes in gene expression. The Chd7 gene, essential for neural crest cell migration and patterning, was found to be hypomethylated in each experimental animal tested compared to water-treated controls. Furthermore, distinct patterns of CpG island methylation yielded novel candidate genes for further investigation.
    Behavioural neurology 10/2015; 2015(1):1-10. DOI:10.1155/2015/426263 · 1.45 Impact Factor
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    • "For environmental toxicant biomarkers, it is difficult to interpret abnormal levels in ASD. For instance, a high burden of aluminum, cadmium, lead, mercury, and arsenic was found in a subgroup of a sample of over 500 patients with ASD (164). Other studies have described decreased levels of some of these heavy metals in urine and in hair samples, which may imply that the body is not excreting the heavy metals adequately (41). "
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    ABSTRACT: Autism spectrum disorders (ASDs) are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression, and measures of the body's metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.
    Frontiers in Psychiatry 08/2014; 5:100. DOI:10.3389/fpsyt.2014.00100
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    • "On the other hand, ASD-specific reductions in GLO1 activity (Fig. 1D) confirm previous results obtained in ASD brains (Junaid et al., 2004) and in schizophrenia (Arai et al., 2010), and point toward an autism-specific negative regulator, largely independent of rs4746 genotype (compare Fig. 1B and C). At least two mechanisms could conceivably account for this ASD-specific reduction in GLO1 activity: (a) zinc deficiency, which may be present in up to 40e50% of ASD children especially prior to 3 years of age (Yasuda et al., 2013); (b) decreased GSH/GSSG ratio due to elevated oxidative stress in ASD brains (Muratore et al., 2013; Palmieri et al., 2010). In fact, GLO1 activity relies upon GSH as its co-factor in the transformation of methylglyoxal to D-lactate, and GSSG reversibly inactivates glyoxalase through glutathionylation at Cys 139 . "
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    ABSTRACT: Glyoxalase I (GLO1) is a homodimeric Zn(2+)-dependent isomerase involved in the detoxification of methylglyoxal and in limiting the formation of advanced glycation end-products (AGE). We previously found the rs4746 A332 (Glu111) allele of the GLO1 gene, which encodes for glyoxalase I, associated with "unaffected sibling" status in families with one or more children affected by Autism Spectrum Disorder (ASD). To identify and characterize this protective allele, we sequenced GLO1 exons and exon-intron junctions, detecting two additional SNPs (rs1049346, rs1130534) in linkage disequilibrium with rs4746. A family-based association study involving 385 simplex and 20 multiplex Italian families yielded a significant association with autism driven only by the rs4746 C332 (Ala111) allele itself (P < 0.05 and P < 0.001 under additive and dominant/recessive models, respectively). Glyoxalase enzymatic activity was significantly reduced both in leukocytes and in post-mortem temporocortical tissue (N = 38 and 13, respectively) of typically developing C332 allele carriers (P < 0.05 and <0.01), with no difference in Glo1 protein levels. Conversely, AGE amounts were significantly higher in the same C332 post-mortem brains (P = 0.001), with a strong negative correlation between glyoxalase activity and AGE levels (τ = -0.588, P < 0.01). Instead, 19 autistic brains show a dysregulation of the glyoxalase-AGE axis (τ = -0.209, P = 0.260), with significant blunting of glyoxalase activity and AGE amounts compared to controls (P < 0.05), and loss of rs4746 genotype effects. In summary, the GLO1 C332 (Ala111) allele confers autism vulnerability by reducing brain glyoxalase activity and enhancing AGE formation, but years after an autism diagnosis the glyoxalase-AGE axis appears profoundly disrupted, with loss of C332 allelic effects.
    Journal of Psychiatric Research 08/2014; 59. DOI:10.1016/j.jpsychires.2014.07.021 · 3.96 Impact Factor
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