Genetic Background Influences Behavior and Responses to Epigenetic Changes Induced by a Methyl-Donor Diet

With recent strides in epigenetics, mainstream media informs the public that we can “beat our genes” by, for instance, changing our diet. Genetics, however, still plays a role in phenotype. Folate and other methyl-donor pathway components are widely supplemented due to their ability to prevent neural tube defects during prenatal development. In addition to vitamins, these compounds are also added to commercial flour, energy drinks, and other supplements. Several lines of evidence suggest that these supplements act through epigenetic mechanisms, including altering DNA methylation. Increasing evidence suggests potential deleterious effects of excessive folate. Given the benefits of these compounds, risk statements must be made with caution. We hypothesized that excess dietary methyl donors during development might contribute to the apparent rise in neurobehavioral disorders such as attention-deficit disorder (ADD), obsessive compulsive disorder (OCD) and autism spectrum disorders (ASD). To test these hypotheses, we used wildderived Peromyscus (deer mice) stocks. Peromyscus are common native North American mammals and exhibit great natural variation. We used two species that are known to differ in physiology, epigenetic control, and behavior. Specifically, P. maniculatus (BW stock) are susceptible to repetitive behaviors and are more aggressive in a neutral space. P. polionotus (PO stock) exhibit greater sociality and less repetitive behavior and are better able to buffer stress. In addition the two species can form fertile hybrids in BW female x PO male crosses thus enabling genetic basis of such phenotypes to be determined. Here we have determined genetic mechanisms by which behaviors differ between BW and PO. Additionally, we discovered behavioral differences in a naturally occurring wide band agouti (ANb) deer mouse (on a BW background) when compared to BW. Using the same methyl-donor diet used in the classic mouse agouti viable yellow allele (Avy), we demonstrated that the effects of the diet are different across three genotypes (while two genotypes, BW and ANb, are very similar). These effects included various adult defects, mortality, and behavioral changes. Here we also present data from additional behavioral parameters in both PO and BW animals developmentally exposed to the methyldonor diet. We also present data showing paternal genotype affects DNA methylation status at the imprinting control region of the Peg10/Sgce locus. This work was funded by NIH P40 OD 010961 and by a SPARC Grant from the Office of the VP for Research at the University of South Carolina

Peromyscus as a Mammalian Epigenetic Model

Deer mice (Peromyscus) offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied. Peromyscus resources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involving Peromyscus models. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using a Peromyscus model of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects, Peromyscus models have a great potential

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

Lake Allatoona Preservation Authority (LAPA) Think Water First Initiative

Proceedings of the 2011 Georgia Water Resources Conference, April 11, 12, and 13, 2011, Athens, Georgia.The Lake Allatoona Preservation Authority (LAPA) mission is to provide stewardship of the Greater Lake Allatoona Watershed in order to restore, preserve and protect water quality and uses beneficial for present and future generations. The newest initiative from LAPA, Think Water First, targets the elected officials who establish regulations concerning development practices within the watershed. LAPA has a long-term vision of expanding the messages to other audiences building on the success of the initial campaign. As a first step, LAPA developed a video to inform elected officials of the impacts that development activities can have on the watershed. Lake Allatoona provides drinking water, recreation, and tourism revenues to the surrounding communities. Water quality impacts from land use changes can negatively impact these important functions and threaten the existing quality of life. The presentation will highlight the recommendations included in the LAPA video, which include; (1) think water first, (2) rein in the runoff, and (3) encourage water sensitive development. Many of these recommendations are based on the principles of low impact design and are intended to reduce water quality impacts associated with new developments. The presentation will also include a showing of the video developed as a part of the Think Water First campaign.Sponsored by: Georgia Environmental Protection Division U.S. Geological Survey, Georgia Water Science Center U.S. Department of Agriculture, Natural Resources Conservation Service Georgia Institute of Technology, Georgia Water Resources Institute The University of Georgia, Water Resources FacultyThis book was published by Warnell School of Forestry and Natural Resources, The University of Georgia, Athens, Georgia 30602-2152. The views and statements advanced in this publication are solely those of the authors and do not represent official views or policies of The University of Georgia, the U.S. Geological Survey, the Georgia Water Research Institute as authorized by the Water Research Institutes Authorization Act of 1990 (P.L. 101-307) or the other conference sponsors

Acute high folic acid treatment in SH-SY5Y cells with and without MTHFR function leads to gene expression changes in epigenetic modifying enzymes, changes in epigenetic marks, and changes in dendritic spine densities.

Epigenetics are known to be involved in various disorders, including neurobiological disorders like autism. Dietary factors such as folic acid can affect epigenetic marks using methylenetetrahydrofolate reductase (MTHFR) to metabolize folic acid to a one-carbon methyl group. As MTHFR mutations are frequent, it is curious as to whether excess folic acid, with or without functioning MTHFR, could affect gene expression, epigenetics, and neuromorphology. Here, we investigated gene expression and activity of epigenetic modifying enzymes, genome-wide DNA methylation, histone 3 modifications, and dendritic spine densities in SH-SY5Y cells with or without a knockdown of MTHFR and with or without an excess of folic acid. We found alterations to gene expression of epigenetic modifying enzymes, including those associated with disorders like autism. Grouping the epigenetic modifying enzymes by function indicated that gene expression was widely affected for genes that code for enzymes affecting DNA methylation, histone acetylation, histone methylation, histone phosphorylation, and histone ubiquitination when excess folic acid treatment occurred with or without the knockdown of MTHFR. MTHFR was significantly reduced upon excess folic acid treatment whether MTHFR was knocked-down or not. Further, methyl-CpG binding protein 2 expression was significantly decreased with excess folic acid treatment with and without proper MTHFR expression. Global DNA methylation decreased due to the knockdown alone while global hydroxymethylated DNA increased due to the knockdown alone. TET2 expression significantly increased with the MTHFR knockdown alone. Excess folic acid alone induced a decrease in TET3 expression. Excess folic acid induced an increase in dendritic spines without the MTHFR knockdown, but folic acid induced a decrease in dendritic spines when MTHFR was knocked-down. The knockdown alone also increased the dendritic spines significantly. Histone 3 acetylation at lysine 18 was significantly increased when excess folic acid was applied to cells with the MTHFR knockdown, as was histone 3 phosphorylation at serine 10. Broadly, our results indicate that excess folic acid, even with functioning MTHFR, could have detrimental effects on cells

Sticks, leaves, buckets, and bowls: Distributional patterns of children's at-home object handling in two subsistence societies

Object-centric interactions provide rich learning moments for young children, including opportunities to discover word meanings. Children’s first-person object handling experiences, in particular, form a key source of input—one that varies across cultures and across development. Using daylong photo streams from child-worn cameras, we analyze >17k images to identify the frequency and targets of child object handling across the first four years in two small-scale subsistence farming communities on opposite sides of the globe (Rossel Papuan and Tseltal Mayan). Overall, we see general consistency in the distribution of object categories (e.g., consumables, mealtime tools, natural objects, etc.) handled by children across cultures and age, likely reflecting stable properties of children’s physical environments and day-to-day routines. However, the exact objects available to children vary both within and across communities and diversify with age. These various distributions of handling patterns are discussed in their relation to potential consequences for early learning

What family support specialists do: examining service delivery.

This study describes services provided by family support specialists (FSS), peer advocates in programs for children with serious psychiatric conditions, to delineate differences between recommended components of FSS services and services actually provided. An analysis of qualitative interview and observational data and quantitative survey data from 63 staff at 21 mental health programs in New York identified that FSS and other staff have generally similar ideas about FSS services, and that these perceptions of activities are generally congruent with what FSS actually did. Implications of findings are discussed in the context of developing competencies and quality indicators for FSS

A Response to Proposed Budget Cuts Affecting Children’s Mental Health: Protecting Policies and Programs That Promote Collective Efficacy

Children stand to lose if the federal government follows through on threats to cut funding for critical safety-net programs that have long supported families and communities. Although cuts directly targeting children’s mental health are a great concern, cuts to policies that support health, housing, education, and family income are equally disturbing. These less publicized proposed cuts affect children indirectly, but they have direct effects on their families and communities. The importance of these services is supported by an extensive body of social learning research that promotes collective efficacy—neighbors positively influencing each other—shown to have positive long-term effects on children’s development and adult outcomes. In this article, the authors describe two federal programs that by virtue of their impact on families and communities are likely to promote collective efficacy and positively affect children’s mental health; both programs are facing severe cutbacks. They suggest that states adopt a cross-system approach to promote policies and programs in general medical health, mental health, housing, education, welfare and social services, and juvenile justice systems as a viable strategy to strengthen families and communities and promote collective efficacy. The overall goal is to advance a comprehensive national mental health policy for children that enhances collaboration across systems and strengthens families and communities, which is especially critical for children living in marginalized communities