scholarly journals Developmental exposure to methylmercury and ADHD, a literature review of epigenetic studies

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Tao Ke ◽  
Alexey A Tinkov ◽  
Antoly V Skalny ◽  
Aaron B Bowman ◽  
Joao B T Rocha ◽  
...  
Keyword(s):  
Dopaminergic System ◽  
Neurodevelopmental Disorder ◽  
Epigenetic Changes ◽  
Mehg Exposure ◽  
Behavioral Alterations ◽  
Functional Changes ◽  
Relevant Evidence ◽  
Increased Risk ◽  
Environmental Causes ◽  
Behavioral Impairments

Abstract Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects the competence of academic performance and social wellness in children and adults. The causes of ADHD are unclear. Both genetic and environmental factors contribute to the development of ADHD. The behavioral impairments in ADHD are associated with epigenetic changes in genes that are important for neurodevelopment. Among environmental causes of ADHD, the neurotoxin methylmercury (MeHg) is associated with an increased risk for ADHD. Developing children are susceptible to neurotoxic effects of prenatal MeHg exposure. Human epidemiology studies have shown that prenatal MeHg exposure could invoke epigenetic changes in genes that are involved in ADHD. In addition, the pathogenesis of ADHD involves dopaminergic system, which is a target of developmental MeHg exposure. MeHg-induced alterations in the dopaminergic system have a profound impact on behavioral functions in adults. As a trace level of MeHg (around nM) can induce long-lasting behavioral alterations, potential mechanisms of MeHg-induced functional changes in the dopaminergic system may involve epigenetic mechanisms. Here, we review the relevant evidence on developmental MeHg exposures and the risk for ADHD. We also point out research gaps in understanding environmental causes of ADHD.

scholarly journals In Silico Exploration of the Potential Role of Acetaminophen and Pesticides in the Etiology of Autism Spectrum Disorder

Toxics ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 97
Author(s):  
Tristan Furnary ◽  
Rolando Garcia-Milian ◽  
Zeyan Liew ◽  
Shannon Whirledge ◽  
Vasilis Vasiliou
Keyword(s):  
Autism Spectrum Disorder ◽  
Prenatal Exposure ◽  
Pesticide Exposure ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Biomedical Literature ◽  
Spectrum Disorder ◽  
Biological Processes ◽  
Genetic Associations ◽  
Increased Risk

Recent epidemiological studies suggest that prenatal exposure to acetaminophen (APAP) is associated with increased risk of Autism Spectrum Disorder (ASD), a neurodevelopmental disorder affecting 1 in 59 children in the US. Maternal and prenatal exposure to pesticides from food and environmental sources have also been implicated to affect fetal neurodevelopment. However, the underlying mechanisms for ASD are so far unknown, likely with complex and multifactorial etiology. The aim of this study was to explore the potential effects of APAP and pesticide exposure on development with regards to the etiology of ASD by highlighting common genes and biological pathways. Genes associated with APAP, pesticides, and ASD through human research were retrieved from molecular and biomedical literature databases. The interaction network of overlapping genetic associations was subjected to network topology analysis and functional annotation of the resulting clusters. These genes were over-represented in pathways and biological processes (FDR p < 0.05) related to apoptosis, metabolism of reactive oxygen species (ROS), and carbohydrate metabolism. Since these three biological processes are frequently implicated in ASD, our findings support the hypothesis that cell death processes and specific metabolic pathways, both of which appear to be targeted by APAP and pesticide exposure, may be involved in the etiology of ASD. This novel exposures-gene-disease database mining might inspire future work on understanding the biological underpinnings of various ASD risk factors.

scholarly journals Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Christina Coughlan ◽  
Douglas I. Walker ◽  
Kelly M. Lohr ◽  
Jason R. Richardson ◽  
Laura M. Saba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pesticide Exposure ◽  
Epidemiological Studies ◽  
Cytoskeletal Proteins ◽  
Synaptic Function ◽  
Behavioral Alterations ◽  
Mechanisms Of Toxicity ◽  
Kegg Pathways ◽  
Increased Risk ◽  
Proteomic Analyses

Epidemiological studies indicate exposures to the herbicide paraquat (PQ) and fungicide maneb (MB) are associated with increased risk of Parkinson’s disease (PD). Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg), MB (30 mg/kg), or the combination of PQ and MB (PQMB). Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration.

Mechanisms involved in developmental programming of hypertension and renal diseases. Gender differences

2014 ◽  
Vol 18 (2) ◽  
Author(s):  
Analia Lorena Tomat ◽  
Francisco Javier Salazar
Keyword(s):  
Metabolic Diseases ◽  
Current Knowledge ◽  
Adult Life ◽  
Developmental Programming ◽  
Renal Diseases ◽  
Future Studies ◽  
Functional Changes ◽  
Regulatory Systems ◽  
Increased Risk ◽  
Renal Changes

AbstractA substantial body of epidemiological and experimental evidence suggests that a poor fetal and neonatal environment may “program” susceptibility in the offspring to later development of cardiovascular, renal and metabolic diseases.This review focuses on current knowledge from the available literature regarding the mechanisms linking an adverse developmental environment with an increased risk for cardiovascular, renal and metabolic diseases in adult life. Moreover, this review highlights important sex-dependent differences in the adaptation to developmental insults.Developmental programming of several diseases is secondary to changes in different mechanisms inducing important alterations in the normal development of several organs that lead to significant changes in birth weight. The different diseases occurring as a consequence of an adverse environment during development are secondary to morphological and functional cardiovascular and renal changes, to epigenetic changes and to an activation of several hormonal and regulatory systems, such as angiotensin II, sympathetic activity, nitric oxide, COX2-derived metabolites, oxidative stress and inflammation. The important sex-dependent differences in the developmental programming of diseases seem to be partly secondary to the effects of sex hormones. Recent studies have shown that the progression of these diseases is accelerated during aging in both sexes.The cardiovascular, renal and metabolic diseases during adult life that occur as a consequence of several insults during fetal and postnatal periods are secondary to multiple structural and functional changes. Future studies are needed in order to prevent the origin and reduce the incidence and consequences of developmental programmed diseases.

scholarly journals Acute small intestinal inflammation results in persistent lymphatic alterations

2018 ◽  
Vol 314 (3) ◽  
pp. G408-G417 ◽  
Author(s):  
Sonia Rehal ◽  
Matthew Stephens ◽  
Simon Roizes ◽  
Shan Liao ◽  
Pierre-Yves von der Weid
Keyword(s):  
Dendritic Cell ◽  
Lymphatic System ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Lymphatic Vessels ◽  
Lymphoid Tissues ◽  
Functional Changes ◽  
Increased Risk ◽  
Small Intestinal ◽  
Acute Ileitis

Inflammatory bowel disease (IBD) has a complex pathophysiology with limited treatments. Structural and functional changes in the intestinal lymphatic system have been associated with the disease, with increased risk of IBD occurrence linked to a history of acute intestinal injury. To examine the potential role of the lymphatic system in inflammation recurrence, we evaluated morphological and functional changes in mouse mucosal and mesenteric lymphatic vessels, and within the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with dextran sodium sulfate (DSS). We monitored whether the changes persisted during a 14-day recovery period and determined their potential consequences on dendritic cell (DC) trafficking between the mucosa and lymphoid tissues. DSS administration was associated with marked lymphatic abnormalities and dysfunctions exemplified by lymphangiectasia and lymphangiogenesis in the ileal mucosa and mesentery, increased mesenteric lymphatic vessel leakage, and lymphadenopathy. Lymphangiogenesis and lymphadenopathy were still evident after recovery from intestinal inflammation and correlated with higher numbers of DCs in mucosal and lymphatic tissues. Specifically, a deficit in CD103+ DCs observed during acute DSS in the lamina propria was reversed and further enhanced during recovery. We concluded that an acute intestinal insult caused alterations of the mesenteric lymphatic system, including lymphangiogenesis, which persisted after resolution of inflammation. These morphological and functional changes could compromise DC function and movement, increasing susceptibility to further gastrointestinal disease. Elucidation of the changes in mesenteric and intestinal lymphatic function should offer key insights for new therapeutic strategies in gastrointestinal disorders such as IBD. NEW & NOTEWORTHY Lymphatic integrity plays a critical role in small intestinal homeostasis. Acute intestinal insult in a mouse model of acute ileitis causes morphological and functional changes in mesenteric and intestinal lymphatic vessels. While some of the changes significantly regressed during inflammation resolution, others persisted, including lymphangiogenesis and altered dendritic cell function and movement, potentially increasing susceptibility to the recurrence of gastrointestinal inflammation.

scholarly journals Oxidative stress underlies heritable impacts of paternal cigarette smoke exposure

2019 ◽  
Author(s):  
Patrick J Murphy ◽  
Jingtao Guo ◽  
Timothy G Jenkins ◽  
Emma R James ◽  
John R Hoidal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Dna Methylation ◽  
Cigarette Smoke ◽  
Cigarette Smoke Exposure ◽  
Epigenetic Changes ◽  
Sperm Dna ◽  
Increased Risk ◽  
Paternal Smoking ◽  
Sperm Dna Methylation

SUMMARYPaternal cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring, but the mechanism has not been identified. This study used mouse models to evaluate: 1) what impact paternal CS exposure has on sperm DNA methylation (DNAme), 2) whether sperm DNAme changes persist after CS exposure ends, 3) the degree to which DNAme and gene expression changes occur in offspring and 4) the mechanism underlying impacts of CS exposure. We demonstrate that CS exposure induces sperm DNAme changes that are partially corrected within 28 days of removal from CS exposure. Additionally, paternal smoking causes changes in neural DNAme and gene expression in offspring. Remarkably, the effects of CS exposure are largely recapitulated in oxidative stress-compromised Nrf2-/- mice and their offspring, independent of paternal smoking. These results demonstrate that paternal CS exposure impacts offspring phenotype and that oxidative stress underlies CS induced heritable epigenetic changes.

scholarly journals Coping with adequate and inadequate self-assessment of older people’s risk of falling: a mixed-methods study in Germany.

2019 ◽  
Author(s):  
Nicole Strutz ◽  
Hanna Brodowski ◽  
Sandra Mümken ◽  
Ursula Müller-Werdan ◽  
Jörn Kiselev
Keyword(s):  
Older People ◽  
Coping Strategies ◽  
Fall Risk ◽  
Qualitative Content Analysis ◽  
Self Awareness ◽  
Risk Of Falling ◽  
Self Assessment ◽  
Functional Changes ◽  
Positive Coping ◽  
Increased Risk

Abstract Background: Older people are exposed to an increased risk of falling due to a multitude of physiological and functional changes and fear of falling. The risk of falling is assessed and managed differently. It should be found out whether the coping strategies of older people differ with regard to their activities in daily life depending on the adequacy of their self-assessed fall risk. Methods: Adequacy of the perceived fall risk was evaluated with the de Morton Mobility Index and the Activities-specific Balance Confidence Scale among 100 older people. Additionally, semi-structured interviews were conducted in 16 participants with an identified fall risk. Coding techniques, based on structuring qualitative content analysis and the half-split method were applied. Results: Six out of 16 interviewees assessed their fall risk adequately. Interviews with the seniors resulted in topics such as coping strategies and awareness and several sub-topics in each category. Participants who adequately assessed their own fall risk reported an “active/positive” coping behavior and awareness of themselves. In contrast, those who assessed their own risk of falling inadequately covered all identified categories with no identifiable pattern. Conclusion: An adequate self-assessment of fall risks is accompanied by positive coping strategies to maintain an active lifestyle. In contrast, a lack of an adequate self-awareness seems to lead to arbitrary coping strategies. Assisting older people in their self-awareness regarding their own fall risk should be emphasized in order to adopt positive coping strategies. Future studies are necessary to better understand the underlying mechanisms that lead to an adequate or inadequate self-assessment in older people fall risk.

scholarly journals Contributing to Understand the Crosstalk between Brain and Periphery in Methylmercury Intoxication: Neurotoxicity and Extracellular Vesicles

2021 ◽  
Vol 22 (19) ◽  
pp. 10855
Author(s):  
Gabriela de Paula Arrifano ◽  
Marcus Augusto-Oliveira ◽  
Megan Sealey-Bright ◽  
Jaezah Zainal ◽  
Luciana Imbiriba ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Human Exposure ◽  
Protective Role ◽  
Behavioral Performance ◽  
Mehg Exposure ◽  
Behavioral Alterations ◽  
Histological Changes ◽  
Molecular Changes ◽  
Male Wistar Rats ◽  
Methylmercury Intoxication

Human exposure to methylmercury (MeHg) is currently high in regions such as the Amazon. Understanding the molecular changes associated with MeHg-induced neurotoxicity and the crosstalk with the periphery is essential to support early diagnoses. This work aimed to evaluate cellular and molecular changes associated with behavioral alterations in MeHg acute exposure and the possible changes in extracellular vesicles (EVs) number and S100β content. Adults male Wistar rats were orally treated with 5 mg/kg for four days. Behavioral performance, molecular and histological changes in the cerebellum, and plasma EVs were assessed. MeHg-intoxicated animals performed significantly worse in behavioral tests. MeHg increased the number of GFAP+ cells and GFAP and S100β mRNA expression in the cerebellum but no change in NeuN+ or IBA-1+ cells number was detected. The number of exosomes isolated from plasma were decreased by the metal. S100B mRNA was detected in circulating plasma EVs cargo in MeHg exposure. Though preliminary, our results suggest astrocytic reactivity is displaying a protective role once there was no neuronal death. Interestingly, the reduction in exosomes number could be a new mechanism associated with MeHg-induced neurotoxicity and plasma EVs could represent a source of future biomarkers in MeHg intoxication.

scholarly journals Using Linked Data to Examine the Epidemiology of All-Cause and Cause-Specific Mortality Following Release from Incarceration in Eleven Countries

2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Rohan Borschmann ◽  
Claire Keen ◽  
Jesse T Young ◽  
Alexander D Love ◽  
Matthew Spittal ◽  
...  
Keyword(s):  
Linked Data ◽  
Mental Health Problems ◽  
Meta Analysis ◽  
Physical And Mental Health ◽  
Relevant Evidence ◽  
Analysis Methodology ◽  
Increased Risk ◽  
Global Epidemiology ◽  
Individual Participant ◽  
Causes And Risk Factors

IntroductionMore than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. Objectives and ApproachWe aimed to comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from incarceration. We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. ResultsUsing linked data from the 29 individual cohorts, the combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. Preliminary analyses indicate a marked elevation in mortality risk following release from incarceration, with this risk beginning on the day of release. At the time of writing, more detailed analyses are underway regarding all-cause and cause-specific deaths – along with risk and protective factors – and findings will be presented at the IPDLN conference in October. Conclusion / ImplicationsThe MARIC consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalised population.

scholarly journals Attention-deficit/hyperactivity disorder and risk for psychiatric and neurodevelopmental disorders in siblings

2018 ◽  
Vol 49 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Elina Jokiranta-Olkoniemi ◽  
Keely Cheslack-Postava ◽  
Petteri Joelsson ◽  
Auli Suominen ◽  
Alan S. Brown ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Population Based ◽  
Autism Spectrum ◽  
Schizophrenia Spectrum Disorders ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
Spectrum Disorders

AbstractBackgroundProbands with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for several psychiatric and neurodevelopmental disorders. The risk of these disorders among the siblings of probands has not been thoroughly assessed in a population-based cohort.MethodsEvery child born in Finland in 1991–2005 and diagnosed with ADHD in 1995–2011 were identified from national registers. Each case was matched with four controls on sex, place, and date of birth. The full siblings of the cases and controls were born in 1981–2007 and diagnosed in 1981–2013. In total, 7369 cases with 12 565 siblings and 23 181 controls with 42 753 siblings were included in the analyses conducted using generalized estimating equations.Results44.2% of the cases and 22.2% of the controls had at least one sibling diagnosed with any psychiatric or neurodevelopmental disorder (risk ratio, RR = 2.1; 95% CI 2.0–2.2). The strongest associations were demonstrated for childhood-onset disorders including ADHD (RR = 5.7; 95% CI 5.1–6.3), conduct and oppositional disorders (RR = 4.0; 95% CI 3.5–4.5), autism spectrum disorders (RR = 3.9; 95% CI 3.3–4.6), other emotional and social interaction disorders (RR = 2.7; 95% CI 2.4–3.1), learning and coordination disorders (RR = 2.6; 95% CI 2.4–2.8), and intellectual disability (RR = 2.4; 95% CI 2.0–2.8). Also, bipolar disorder, unipolar mood disorders, schizophrenia spectrum disorders, other neurotic and personality disorders, substance abuse disorders, and anxiety disorders occurred at increased frequency among the siblings of cases.ConclusionsThe results offer potential utility for early identification of neurodevelopmental and psychiatric disorders in at-risk siblings of ADHD probands and also argue for more studies on common etiologies.

Psychotropic Drugs in Pregnancy and Lactation

PEDIATRICS ◽  
1982 ◽  
Vol 69 (2) ◽  
pp. 241-244
Author(s):  
Sydney Segal ◽  
Albert W. Pruitt ◽  
Walter R. Anyan ◽  
Reba M. Hill ◽  
Ralph E. Kauffman ◽  
...  
Keyword(s):  
Psychotropic Drugs ◽  
Structural Changes ◽  
Drug Exposure ◽  
Final Decision ◽  
Behavioral Alterations ◽  
Drug Dosing ◽  
Behavioral Studies ◽  
Increased Risk ◽  
Pregnancy And Lactation

Accurate prediction of fetal/neonatal risks following maternal psychotropic drug consumption by the human will require much additional study. Based upon our present understanding of fetal exposure to psychotropic drugs, there would appear to be an increased risk for spontaneous malformations in the case of lithium. There have been inconsistent reports of structural abnormalities following exposure to phenothiazines and benzodiazepines. In animal models that demonstrate structural changes due to neuroleptic exposure, in general, extremely large dosages of medication had been given. Thus, their correlative value is limited. Behavioral alterations in animals following drug exposure during pregnancy tend to support increased concerns about the safety of psychotropic drugs for the fetus but cannot be used alone in making a final decision. Behavioral studies evaluating drugs in breast milk have been restricted to experimental animals; hence, the associated risks from this form of drug dosing in man remain unknown. At present, neither gross anatomic nor motor side effects have been apparent in the infant. The question of the development of subtle behavioral changes as a long-term consequence will remain undetermined until careful assessments have been completed.

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