Autism-Like Behavior and Epigenetic Changes Associated with Autism as Consequences ofIn UteroExposure to Environmental Pollutants in a Mouse Model

We tested the hypothesis thatin uteroexposure 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 uteroexposure 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.

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Faculty Opinions recommendation of De novo CpG island methylation in human cancer cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1030634.360425 ◽

2006 ◽

Author(s):

Frank Lyko

Keyword(s):

Cancer Cells ◽

De Novo ◽

Cpg Island ◽

Human Cancer ◽

Human Cancer Cells ◽

Cpg Island Methylation

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EPEGENTIC TOXICOLOGY: PERSPECTIVES OF THE DEVELOPMENT

Токсикологический вестник ◽

10.36946/0869-7922-2018-1-2-7 ◽

2018 ◽

pp. 2-7

Author(s):

G. A. Sofronov ◽

E. L. Patkin

Keyword(s):

Public Health ◽

Life Cycle ◽

Human Health ◽

Chronic Exposure ◽

Environmental Pollutants ◽

Epigenetic Mechanisms ◽

Epigenetic Changes ◽

Mechanism Of Formation ◽

Health Disorders ◽

Time Periods

One of the complex problems of modern experimental toxicology remains the molecular mechanism of formation of human health disorders separated at different time periods from acute or chronic exposure to toxic environmental pollutants (ecotoxicants). Identifying and understanding what epigenetic changes are induced by the environment, and how they can lead to unfavorable outcome, are vital for protecting public health. Therefore, we consider it important a modern understanding of epigenetic mechanisms involved in the life cycle of mammals and assess available data on the environmentally caused epigenetic toxicity and, accordingly fledging epigenenomic (epigenetic) regulatory toxicology.

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Contamination of Heavy Metals, Polychlorinated Dibenzo-p-Dioxins/Furans and Dioxin-Like Polychlorinated Biphenyls in Wharf Roach Ligia spp. In Japanese Intertidal and Supratidal Zones

Applied Sciences ◽

10.3390/app11041856 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1856

Author(s):

Masato Honda ◽

Xuchun Qiu ◽

Suzanne Lydia Undap ◽

Takeshi Kimura ◽

Tsuguhide Hori ◽

...

Keyword(s):

Heavy Metals ◽

Polychlorinated Biphenyls ◽

Limit Of Detection ◽

Environmental Pollutants ◽

Dry Weight ◽

Polychlorinated Dibenzofurans ◽

Environmental Indicator ◽

Pollution Levels ◽

Copper Zinc ◽

Total Concentrations

We investigated the pollution levels of 6 heavy metals and 29 dioxins (polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs)) in intertidal and supratidal zones by using wharf roaches (Ligia spp.) collected from 12 sampling sites on the coast of Northeast Japan from November 2011 to June 2012. The total concentrations of heavy metals ranged from 177 to 377 µg/g-dry weight (dw), and the predominant metals were copper, zinc, and aluminum. The order of the detected level of heavy metals was zinc > aluminum > copper > cadmium > lead > chromium, and this trend was similar to a previous report. The total toxic equivalent (TEQ) value of the PCDD/Fs ranged from less than the limit of detection (<LOD) to 2.33 pg-TEQ/g-dw, and the predominant congener was octachlorodibenzodioxin (<LOD to 110 pg/g-dw). Compared with PCDD/Fs, DL-PCBs were detected at a predominantly higher level (total TEQ value: 0.64–27.79 pg-TEQ/g-dw). Detected levels of dioxins, especially DL-PCBs in the wharf roach, were like those in the bivalves. These results indicate that the wharf roach could reflect heavy metals and dioxin pollution in the supratidal zones and is a suitable environmental indicator for these environmental pollutants. This is the first study to investigate heavy metals, PCDD/Fs, and DL-PCBs pollution in coastal isopods in Japan.

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Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma

BMC Cancer ◽

10.1186/1471-2407-14-101 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 8

Author(s):

Inga Peters ◽

Natalia Dubrowinskaja ◽

Michael Kogosov ◽

Mahmoud Abbas ◽

Jörg Hennenlotter ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Mrna Expression ◽

Renal Cell ◽

Clear Cell ◽

Cpg Island ◽

Recurrence Free Survival ◽

Cell Renal Cell Carcinoma ◽

Free Survival ◽

Cpg Island Methylation

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Protective Effects of Dendrobium nobile Lindl. Alkaloids on Alzheimer's Disease-like Symptoms Induced by High-methionine Diet

Current Neuropharmacology ◽

10.2174/1570159x19666210809101945 ◽

2021 ◽

Vol 19 ◽

Author(s):

Tingting Pi ◽

Guangping Lang ◽

Bo Liu ◽

Jingshan Shi

Keyword(s):

Alzheimer’S Disease ◽

Learning And Memory ◽

Morris Water Maze ◽

Water Maze ◽

Cpg Island ◽

Morris Water Maze Test ◽

Dendrobium Nobile ◽

Maze Test ◽

Neuron Damage ◽

Cpg Island Methylation

Background: High methionine-diet (HMD) causes Alzheimer's disease (AD)-like symptoms. Previous studies have shown that Dendrobium nobile Lindle. alkaloids (DNLA) had potential benefits for AD. Object: Whether DNLA can improve AD-like symptoms induced by HMD is to be explored. Method: Mice were fed with 2% HMD diet for 11 weeks, the DNLA20 control group (20 mg/kg), DNLA10 group (10 mg/kg), and DNLA20 group (20 mg/kg) were administrated with DNLA for 3 months. Morris water maze test was used to detect learning and memory ability. Neuron damage was evaluated by HE and Nissl stainings. Levels of homocysteine (Hcy), beta-amyloid 1-42 (Aβ1-42), S-adenosine methionine (SAM), and S-adenosine homocysteine (SAH) were detected by ELISA. Immunofluorescence and western blotting (WB) were used to determine the expression of proteins. CPG island methylation. Results: Morris water maze test revealed that DNLA improved learning and memory dysfunction. HE, Nissl, and immunofluorescence stainings showed that DNLA alleviated neuron damage and reduced the 5-methylcytosine (5-mC), Aβ1-40, and Aβ1-42 levels. DNLA also decreased the levels of Hcy and Aβ1-42 in the serum, along with decreased SAM/SAH levels in the liver tissue. WB results showed that DNLA down-regulated the expression of the amyloid-precursor protein (APP), presenilin-1 (PS1), beta-secretase-1 (BACE1), DNA methyltransferase1 (DNMT1), Aβ1-40, and Aβ1-42 proteins. DNLA also up-regulated the expression of the protein of insulin-degrading enzyme (IDE), neprilysin (NEP), DNMT3a, and DNMT3b. Meanwhile, DNLA increased CPG island methylation levels of APP and BACE1 genes. Conclusions: DNLA alleviated AD-like symptoms induced by HMD via the DNA methylation pathway.

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