Mobile phone use, blood lead levels, and attention deficit hyperactivity symptoms in children: a longitudinal study.

BACKGROUND: Concerns have developed for the possible negative health effects of radiofrequency electromagnetic field (RF-EMF) exposure to children's brains. The purpose of this longitudinal study was to investigate the association between mobile phone use and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) considering the modifying effect of lead exposure. METHODS: A total of 2,422 children at 27 elementary schools in 10 Korean cities were examined and followed up 2 years later. Parents or guardians were administered a questionnaire including the Korean version of the ADHD rating scale and questions about mobile phone use, as well as socio-demographic factors. The ADHD symptom risk for mobile phone use was estimated at two time points using logistic regression and combined over 2 years using the generalized estimating equation model with repeatedly measured variables of mobile phone use, blood lead, and ADHD symptoms, adjusted for covariates. RESULTS: The ADHD symptom risk associated with mobile phone use for voice calls but the association was limited to children exposed to relatively high lead. CONCLUSIONS: The results suggest that simultaneous exposure to lead and RF from mobile phone use was associated with increased ADHD symptom risk, although possible reverse causality could not be ruled out

Effects of Silibinin Against Prothrombin Kringle-2-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System In Vivo

Parkinson's disease (PD) and Alzheimer's disease exhibit common features of neurodegenerative diseases and can be caused by numerous factors. A common feature of these diseases is neurotoxic inflammation by activated microglia, indicating that regulation of microglial activation is a potential mechanism for preserving neurons in the adult brain. Recently, we reported that upregulation of prothrombin kringle-2 (pKr-2), one of the domains that make up prothrombin and which is cleaved and generated by active thrombin, induces nigral dopaminergic (DA) neuronal death through neurotoxic microglial activation in the adult brain. In this study, we show that silibinin, a flavonoid found in milk thistle, can suppress the production of inducible nitric oxide synthase and neurotoxic inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, after pKr-2 treatment by downregulating the extracellular signal-regulated kinase signaling pathway in the mouse substantia nigra. Moreover, as demonstrated by immunohistochemical staining, measurements of the dopamine and metabolite levels, and open-field behavioral tests, silibinin treatment protected the nigrostriatal DA system resulting from the occurrence of pKr-2-triggered neurotoxic inflammation in vivo. Thus, we conclude that silibinin may be beneficial as a natural compound with anti-inflammatory effects against pKr-2-triggered neurotoxicity to protect the nigrostriatal DA pathway and its properties, and thus, may be applicable for PD therapy. © 2019, Mary Ann Liebert, Inc.1

Number of children participating in the CHEER study by survey years.

<p>Of 2,516 children at baseline in 2008 and 2010 shown as the dotted lined box, 2,422 were included after excluding children with incomplete questionnaire responses on mobile phone use or a lack of blood lead measurements in 2008 and 2010.</p

Association Between Mobile Phone Use and ADHD in Children Stratified by the Blood Lead Level in 2008 and 2010, Korea, the CHEER study.

<p>CHEER, Children’s Health and Environmental Health Research, ADHD, Attention Deficit Hyperactivity Disorder.</p><p>Odds ratios and 95% confidence intervals were estimated using the generalized estimating equation model adjusted for age, gender, number of siblings, area, household income, maternal smoking during pregnancy, child’s history of neuropsychiatric illness, parental marital status, and parental history of neuropsychiatric disease as time-independent covariates.</p><p>p-trend calculated using the ordinal scale of the variable in the corresponding model.</p><p>The cut-off point of the high and low groups was the upper 25 percentile of the distribution of the higher between two blood lead levels in 2008 and 2010.</p><p>p for multiplicative interaction between blood lead level (high vs. low) and time-varying variables of mobile phone use as a continuous scale.</p>*<p>Among children who owned a mobile phone.</p

Characteristics and Mobile Phone Use Patterns of Children in 2008 to 2010, Korea, the CHEER study.

<p>CHEER, Children’s Health and Environmental Health Research, ADHD, Attention Deficit Hyperactivity Disorder. 1 USD equals approximately 1,084.5 KRW as of 8/9/2011.</p>*<p>Among children who owned a mobile phone.</p

Changes in ADHD symptoms according to the change in mobile phone use for voice calls and playing game over 2 years.

<p>Numbers in parentheses are the number of subjects in the corresponding group.</p

Simultaneous Model of Mobile Phone Use Variables Associated with ADHD in Children Stratified by the Blood Lead Level, 2008–2010, Korea, the CHEER study.

<p>CHEER, Children’s Health and Environmental Health Research, ADHD, Attention Deficit Hyperactivity Disorder.</p><p>Odds ratios and 95% confidence intervals estimated using the generalized estimating equation model including three mobile phone use variables and simultaneously adjusted for age, gender, number of siblings, area, household income, maternal smoking during pregnancy, child’s history of neuropsychiatric illness, and parental marital status as time-independent covariates.</p><p>p-trend calculated using the ordinal scale of the variable in the corresponding model.</p><p>The cut-off point of the high and low groups was the upper 25 percentile of the distribution of the higher levels between two blood lead levels in 2008 and 2010.</p><p>p for multiplicative interaction between blood lead level (high vs. low) and time-varying variables of mobile phone use as a continuous scale.</p>*<p>Among children who owned a mobile phone.</p

Control of hippocampal prothrombin kringle-2 (pKr-2) expression reduces neurotoxic symptoms in five familial Alzheimer's disease mice

Background and Purpose: There is a scarcity of information regarding the role of prothrombin kringle-2 (pKr-2), which can be generated by active thrombin, in hippocampal neurodegeneration and Alzheimer's disease (AD). Experimental Approach: To assess the role of pKr-2 in association with the neurotoxic symptoms of AD, we determined pKr-2 protein levels in post-mortem hippocampal tissues of patients with AD and the hippocampi of five familial AD (5XFAD) mice compared with those of age-matched controls and wild-type (WT) mice, respectively. In addition, we investigated whether the hippocampal neurodegeneration and object memory impairments shown in 5XFAD mice were mediated by changes to pKr-2 up-regulation. Key Results: Our results demonstrated that pKr-2 was up-regulated in the hippocampi of patients with AD and 5XFAD mice, but was not associated with amyloid-β aggregation in 5XFAD mice. The up-regulation of pKr-2 expression was inhibited by preservation of the blood–brain barrier (BBB) via addition of caffeine to their water supply or by treatment with rivaroxaban, an inhibitor of factor Xa that is associated with thrombin production. Moreover, the prevention of up-regulation of pKr-2 expression reduced neurotoxic symptoms, such as hippocampal neurodegeneration and object recognition decline due to neurotoxic inflammatory responses in 5XFAD mice. Conclusion and Implications: We identified a novel pathological mechanism of AD mediated by abnormal accumulation of pKr-2, which functions as an important pathogenic factor in the adult brain via blood brain barrier (BBB) breakdown. Thus, pKr-2 represents a novel target for AD therapeutic strategies and those for related conditions. © 2021 The Authors. British Journal of Pharmacology published by John Wiley &amp; Sons Ltd on behalf of British Pharmacological Society.TRU