Showing posts with label Neurodevelopmental. Show all posts

Plastic chemical linked to smaller prefrontal cortex, reduced cognitive ability in rats: Findings demonstrate long-term influence of endocrine-disrupting compounds on brain development -- ScienceDaily

Adult rats that had been exposed before birth and during nursing to a
mixture of chemicals (Phthalates) found in a wide range of consumer products have a
smaller medial prefrontal cortex (mPFC) and perform worse on an
attention-switching task than rats not exposed to the chemicals early in
life. These findings, published in JNeurosci, demonstrate a long-term influence of endocrine-disrupting compounds on brain development.

Daniel G. Kougias, Elli P. Sellinger, Jari Willing, Janice M. Juraska. Perinatal
exposure to an environmentally relevant mixture of phthalates results
in a lower number of neurons and synapses in the medial prefrontal
cortex and decreased cognitive flexibility in adult male and female rats. The Journal of Neuroscience, 2018; 0607-18 DOI: 10.1523/JNEUROSCI.0607-18.2018

Brain development disorders in children linked to common environmental toxin exposures -- ScienceDaily

Exposures of pregnant women and children to common
thyroid-hormone-disrupting toxins may be linked to the increased
incidence of brain development disorders, according to a review
published in Endocrine Connections. The review describes how
numerous, common chemicals can interfere with normal thyroid hormone
actions, which are essential for normal brain development in foetuses
and young children, and suggests a need for greater public health
intervention.

Here's the paper from "Endocrine connections":-

Thyroid disrupting chemicals and brain development: an update

A Human Mixture Risk Assessment for Neurodevelopmental Toxicity Associated with Polybrominated Diphenyl Ethers Used as Flame Retardants

"BACKGROUND:
The European Food Safety Authority recently concluded that the exposure of small children (1–3 y old) to brominated diphenyl ether (BDE)-99 may exceed acceptable levels defined in relation to neurodevelopmental toxicity in rodents. The flame retardant BDE-209 may release BDE-99 and other lower brominated BDEs through biotic and abiotic degradation, and all age groups are exposed not only to BDE-209 and -99 but also to a cocktail of BDE congeners with evidence of neurodevelopmental toxicity. The possible risks from combined exposures to these substances have not been evaluated.

OBJECTIVES:
We performed a congener-specific mixture risk assessment (MRA) of human exposure to combinations of BDE-209 and other BDEs based on estimated exposures via diet and dust intake and on measured levels in biologic samples.

METHODS:
We employed the Hazard Index (HI) method by using BDE congener-specific reference doses for neurodevelopmental toxicity.

RESULTS:
Our HI analysis suggests that combined exposures to polybrominated diphenyl ethers (PBDEs) may exceed acceptable levels in breastfeeding infants (0–3 mo old) and in small children (1–3 y old), even for moderate (vs. high) exposure scenarios. Our estimates also suggest that acceptable levels of combined PBDEs may be exceeded in adults whose diets are high in fish. Small children had the highest combined exposures, with some estimated body burdens that were similar to body burdens associated with developmental neurotoxicity in rodents.

CONCLUSIONS:
Our estimates corroborate reports from several recent epidemiological studies of associations between PBDE exposures and neurobehavioral outcomes, and they support the inclusion of BDE-209 in the persistent organic pollutant (POP) convention as well as the need for strategies to reduce exposures to PBDE mixtures, including maximum residue limits for PBDEs in food and measures for limiting the release of PBDEs from consumer waste. "

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Banned chemicals pass through umbilical cord from mother to baby, research finds

"Trace amounts of flame retardants, banned in the U.S. for more than a decade, are still being passed through umbilical cord blood from mothers to their babies, according to new Indiana University research. The chemicals are linked to health concerns including hormone disruption and low birth weight.
PBDEs, or polybrominated diphenyl ethers, were commonly used flame retardants in building materials, electronics and textiles until they were banned in 2004. The chemicals leach into the environment, where they persist and are found today in virtually every population worldwide."

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Is acetaminophen in pregnancy linked to behavioral problems in offspring? - Medical News Today

The findings indicate that children born to women who used of acetaminophen (paracetamol) at 18 and 32 weeks of pregnancy were more likely to have behavioral problems and to be hyperactive. Those whose mothers used acetaminophen at 32 weeks of pregnancy were more likely to have emotional and other challenges.

Pubmed acetaminophen + autism or acetaminophen + ADHD

Project TENDR: Targeting Environmental Neuro-Developmental Risks. The TENDR Consensus Statement

SUMMARY: Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented.

APPROACH: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects.

CONCLUSION: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential."

Fossil fuel combustion endangers children's health in two significant ways: A scientist reviews the evidence

Writing in a commentary in Environmental Health Perspectives, Frederica Perera, director of the Columbia Center for Children's Environmental Health (CCCEH), identifies fossil fuel combustion and associated air pollution and carbon dioxide (CO2) as the root cause of much of the ill health of children today. Because of their inherent biological vulnerability, children now bear a disproportionate burden of disease from both pollution and climate change.

Among the conclusions: by reducing air pollution we will see fewer babies born at low birth weight, and fewer children suffering from asthma and neurodevelopmental problems such as lower IQ and ADHD. Lowered emissions of CO2 and mitigation of climate change will reduce the number of children dying as a result of floods and drought, and fewer children will suffer from heat stress, malnutrition, infectious disease, respiratory illness, and mental illness from displacement, social, and political instability.

Nature Brain disorders across the lifespan

Brain and other nervous-system disorders impose a disproportionate burden on those in low- and middle-income countries. For over a decade, the Fogarty International Center and its NIH partners have supported research and capacity-building to provide context-sensitive solutions to this public health challenge. This supplement outlines the overarching and intersecting research priorities for addressing causes, prevention, treatment and rehabilitation, as well as opportunities to strengthen scientific capacity that can promote global nervous system health."

Free open access supplement:

Seroprevalence of Toxoplasma gondii infection among patients with non-schizophrenic neurodevelopmental disorders in Alexandria, Egypt

"Toxoplasma gondii is an opportunistic parasite with neurotropic characteristics that can mediate neurodevelopmental disorders, including mental, behavioral and personality aspects of their hosts. Therefore, the seroprevalence of anti-Toxoplasma antibodies has been studied in patients with different neurological disorders from different localities. On searching online databases, however, we could not find published studies on the seroprevalence of anti-Toxoplasma antibodies among patients with neurodevelopmental disorders in Egypt. Therefore, the present preliminary study was conducted to determine the serological profile of T. gondii infection among patients with non-schizophrenic neurodevelopmental disorders in Alexandria, Egypt. Data and blood samples were collected from 188 patients recruited for the study from four mental rehabilitation centers in the period from July 2014 to March 2015. The overall seropositivity rates of IgM and IgG among patients were 16.5% (31/188) and 50.0% (94/188), respectively. Of the studied patients' characteristics, only age was significantly associated with anti-Toxoplasma IgG seropositivity, with older patients being about twice more likely exposed to infection. However, no statistically significant association was found with IgM. In addition, seropositivity of anti-Toxoplasma IgG, but not IgM, was significantly associated with non-schizophrenic neurodevelopmental disorders; however, neither IgG nor IgM showed a significant association with cognitive impairment as indicated by the intelligence quotient scores."

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The tantalizing links between gut microbes and the brain : Nature News & Comment

Neuroscientists are probing the idea that intestinal microbiota might influence brain development and behaviour.

Pyrethroid insecticide exposure and cognitive developmental disabilities in children: The PELAGIE mother–child cohort

Pyrethroid insecticides are widely used in agriculture

and in homes. Despite the neurotoxicity of these insecticides at high
doses, few studies have examined whether lower-level exposures could
adversely affect children's neurodevelopment.

The PELAGIE cohort included 3421 pregnant women from Brittany, France
between 2002 and 2006. When their children reached their sixth birthday,
428 mothers from the cohort were randomly selected, successfully
contacted and found eligible. A total of 287 (67%) mothers agreed to
participate with their children in the neuropsychological follow-up. Two
cognitive domains were assessed by the Wechsler Intelligence Scale for
Children: verbal comprehension and working memory. Five pyrethroid and
two organophosphate insecticide metabolites were measured in maternal
and child first-void urine samples collected between 6 and 19
gestational weeks and at 6 years of age, respectively. Linear regression
models were used to estimate associations between cognitive scores and
urinary pyrethroid metabolite concentrations, adjusting for
organophosphate metabolite concentrations and potential confounders.

Maternal prenatal pyrethroid metabolite concentrations were not consistently
associated with any children's cognitive scores. By contrast, childhood
3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend = 0.04 and P-trend < 0.01, respectively) and with working memory scores (P-trend = 0.05 and P-trend < 0.01,
respectively). No associations were observed for the three other
childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA).

Low-level childhood exposures to deltamethrin (as cis-DBCA
is its principal and selective metabolite), in particular, and to
pyrethroid insecticides, in general (as reflected in levels of the 3-PBA
metabolite) may negatively affect neurocognitive development by 6 years
of age. Whatever their etiology, these cognitive deficits may be of
importance educationally, because cognitive impairments in children
interfere with learning and social development. Potential causes that
can be prevented are of paramount public health importance.

A large amount of mitochondrial toxic agents cross the placenta barrier

Researchers from the Hospital Clinic of Barcelona (Spain) have reviewed ten years' worth of scientific studies on mitochondrial toxicity in pregnant women. Exposure to toxic agents such as viruses, certain drugs, pesticides, alcohol and tobacco cause mitochondrial diseases about which very little is known, and which are transmitted from the mother to the foetus. Mitochondria can also suffer acquired pathologies due to, for example, exposure to toxic agents transferred from mother to child, causing conditions such as muscle weakness, inflammation of the pancreas and changes in the distribution and amount of body fat.

A team from the Muscle Research and Mitochondrial Function Laboratory at the Hospital Clinic of Barcelona has reviewed the little information there is available on mitochondrial toxicity in pregnant women over the last ten years. Their report, published in the International Journal of Environmental Research and Public Health, reviews more than 100 studies from the Pubmed/MEDLINE database.

In the report, the researchers propose alternatives in order to avoid any harmful effects for pregnant women and their babies based on two strategies: the search for toxicity markers and the avoidance of any contact with mitochondrial toxic agents.

Prenatal Expression Patterns of Genes Associated With Neuropsychiatric Disorders

OBJECTIVE Neurodevelopmental disorders presumably involve events that
occur during brain development. The authors hypothesized that
neuropsychiatric disorders considered to be developmental in etiology
are associated with susceptibility genes that are relatively upregulated
during fetal life (i.e., differentially expressed). METHOD The authors
investigated the presence of prenatal expression enrichment of
susceptibility genes systematically, as composite gene sets associated
with six neuropsychiatric disorders in the microarray-based "BrainCloud"
dorsolateral prefrontal cortex transcriptome. RESULTS Using a
fetal/postnatal log2-fold change threshold of 0.5, genes associated with
syndromic neurodevelopmental disorders (N=31 genes, p=3.37×10-3),
intellectual disability (N=88 genes, p=5.53×10-3), and autism spectrum
disorder (N=242 genes, p=3.45×10-4) were relatively enriched in prenatal
transcript abundance, compared with the overall transcriptome. Genes
associated with schizophrenia by genome-wide association studies were
not preferentially fetally expressed (N=106 genes, p=0.46), nor were
genes associated with schizophrenia by exome sequencing (N=212 genes,
p=0.21), but specific genes within copy-number variant regions
associated with schizophrenia were relatively enriched in prenatal
transcript abundance, and genes associated with schizophrenia by
meta-analysis were functionally enriched for some neurodevelopmental
processes. In contrast, genes associated with neurodegenerative
disorders were significantly underexpressed during fetal life (N=46
genes, p=1.67×10-3). CONCLUSIONS The authors found evidence for relative
prenatal enrichment of putative susceptibility genes for syndromic
neurodevelopmental disorders, intellectual disability, and autism
spectrum disorder. Future transcriptome-level association studies should
evaluate regions other than the dorsolateral prefrontal cortex, at
other time points, and incorporate further RNA sequencing analyses.

Industrial chemicals 'may cause global neurodevelopmental epidemic' - Medical News Today

According to Dr. Phillippe Grandjean, of the Harvard School of Public Health in Boston, MA, and Dr. Phillip Landrigan, of the Mount Sinai School of Medicine in New York, the number of chemicals that are recognized to be linked with neurodevelopmental disorders has increased
from six to 12.
In 2006, lead, methylmercury, arsenic, polychlorinated bipenyls and toluene were the only chemicals linked to brain development disorders. By last year, manganese, fluoride, chlorpyrifos (a pesticide),
dichlorodiphenyltrichloroethane (DDT), tetrachloroethylene (a solvent), and the polybrominated diphenyl ethers (flame retardants) were added to the list.
These have variously been associated with ADHD, autism , cerebral palsy and dyslexia (and obesity).

The Environmental Neurotoxicant PCB 95 Promotes Synaptogenesis via Ryanodine Receptor-Dependent miR132 Upregulation

Non–dioxin-like (NDL) polychlorinated biphenyls (PCBs) are widespread environmental contaminants linked to neuropsychological dysfunction in children. NDL PCBs increase spontaneous Ca²⁺ oscillations in neurons by stabilizing ryanodine receptor (RyR) calcium release channels in the open configuration, which results in CREB-dependent dendritic outgrowth. In this study, we address the question of whether activation of CREB by NDL PCBs also triggers dendritic spine formation. Nanomolar concentrations of PCB 95, a NDL congener with potent RyR activity, significantly increased spine density and the frequency of miniature EPSCs in primary dissociated rat hippocampal cultures coincident with upregulation of miR132. Inhibition of RyR, CREB, or miR132 as well as expression of a mutant p250GAP cDNA construct that is not suppressed by miR132 blocked PCB 95 effects on spines and miniature EPSCs. PCB 95 also induced spine formation via RyR- and miR132-dependent mechanisms in hippocampal slice cultures. These data demonstrate a novel mechanism of PCB developmental neurotoxicity whereby RyR sensitization modulates spine formation and synaptogenesis via CREB-mediated miR132 upregulation, which in turn suppresses the translation of p250GAP, a negative regulator of synaptogenesis. In light of recent evidence implicating miR132 dysregulation in Rett syndrome and schizophrenia, these findings identify NDL PCBs as potential environmental risk factors for neurodevelopmental disorders

DNA Hydroxymethylation and Neuron Development |EpiBeat

It has been well known for many years that DNA methylation plays many roles in gene regulation and can direct different cell pathways such as apoptosis, differentiation, cancer, and aging. Although DNA methylation can be extremely stable – able to persist through multiple generations – it can also be quite dynamic and able to change in response to a cell’s internal and external environment. More recently, an additional DNA modification, hydroxymethylation, has received much attention. Methylcytosine (5mC) can be oxidized to generate hydroxymethylcytosine (5hmC), which some researchers think is an intermediate in the DNA de-methylation pathway. Unlike 5mC, which is found in approximately equal levels throughout all tissues in the body, 5hmC is most abundantly expressed in the brain and CNS compared to other tissues in the body. This has led many to speculate that 5hmC is more than just a passive mark, and may have its own unique biological functions.

Two neonicotinoid insecticides a risk for human nervous system: EU

The findings were based on recent research and existing data on "the potential of acetamiprid and imidacloprid to damage the developing human nervous system—in particular the brain."
The research suggested the two insecticides "may adversely affect the development of neurons and brain structures associated with functions such as learning and memory," EFSA said in a statement.
"It concluded that some current guidance levels for acceptable exposure ... may not be protective enough to safeguard against developmental neurotoxicity and should be reduced," the EFSA added.

Prenatal exposure to alcohol disrupts brain circuitry: No safe level of drinking during pregnancy, neuroscientist says

In a groundbreaking study, the UC Riverside team discovered that prenatal exposure to alcohol significantly altered the expression of genes and the development of a network of connections in the neocortex -- the part of the brain responsible for high-level thought and cognition, vision, hearing, touch, balance, motor skills, language, and emotion -- in a mouse model of foetal alcohol spectrum disorders. . Prenatal exposure caused wrong areas of the brain to be connected with each other, the researchers found.

Maternal infection and foetal brain development -- -- Science Signaling

Infection of expecting mothers is a putative risk factor for neuropsychiatric disease in human progeny. Infection triggers pro-inflammatory signals, and if prenatal exposure to inflammation creates enduring neurological changes then pro-inflammatory cytokines, such as interleukin-6 (IL-6), could impact fetal brain development (see Cope and Gould). In mice, inhibition of the pro-inflammatory cytokine (IL-6) in pregnant dams injected with a reagent that stimulates antiviral signaling can ameliorate brain defects and behavioral abnormalities in postnatal pups. Gallagheret al. found that two-month-old offspring of pregnant mice injected with a single bolus of IL-6 had increased numbers of proliferating neural progenitor cells (NPCs) in the forebrain subventricular zone (SVZ) as well as increased numbers of olfactory interneurons, which differentiate from these cells. Forebrain precursor cells in fetal brains 1 day after maternal injection of IL-6 or cultured forebrain precursor cells treated acutely with IL-6 exhibited increased cell proliferation and phosphorylation of STAT3 (signal transducer and activator of transcription 3), a target of IL-6 receptor (IL6R) activation. The number of neurosphere-initiating cells and the ability to grow secondary neurospheres after passage in culture was enhanced for SVZ NPCs from brains of postnatal day 7 pups from IL-6–injected dams. Endogenous IL-6 was secreted into the media of cultured embryonic cortical precursor cells, and incubating these cells with a function-blocking IL-6 antibody reduced proliferation. The forebrains of Il6-knockout mice had fewer proliferating precursors, and the precursor cells had reduced ability to form primary and secondary neurospheres in culture. Knockdown of IL6R by siRNA-electroporation in vivo reduced the number of embryonic forebrain precursor cells and increased the number of neurons. Thus, maternal IL-6 exposure enhanced the endogenous IL-6 signaling pathway that is required to promote embryonic forebrain precursor cell self-renewal and prevent premature neuronal differentiation and could be a factor in neurological disease caused by maternal infection.

Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study

Background Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of foetal paracetamol exposure are lacking.

Method Between 1999 and 2008 all pregnant Norwegian women were eligible for recruitment into the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and at 6 months postpartum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire by May 2011. Within this sample were 2919 same-sex sibling pairs who were used to adjust for familial and genetic factors. We modelled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behaviour problems, and temperament (emotionality, activity, sociability and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections and co-medication use during pregnancy.

Results The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development [β 0.24, 95% confidence interval (CI) 0.12–0.51], communication (β 0.20, 95% CI 0.01–0.39), externalizing behaviour (β 0.28, 95% CI 0.15–0.42), internalizing behaviour (β 0.14, 95% CI 0.01–0.28), and higher activity levels (β 0.24, 95% CI 0.11–0.38). Children exposed prenatally to short-term use of paracetamol (1–27 days) also had poorer gross motor outcomes (β 0.10, 95% CI 0.02–0.19), but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes.

Conclusion Children exposed to long-term use of paracetamol during pregnancy had substantially adverse developmental outcomes at 3 years of age.

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