scholarly journals EDCs Reorganize Brain-Behavior Phenotypic Relationships in Rats

2021 ◽  
Vol 5 (5) ◽  
Author(s):  
Morgan E Hernandez Scudder ◽  
Rebecca L Young ◽  
Lindsay M Thompson ◽  
Pragati Kore ◽  
David Crews ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Preference ◽  
Endocrine Disrupting Chemicals ◽  
Preference Test ◽  
Brain Regions ◽  
Behavioral Deficits ◽  
Developmental Exposure ◽  
Individual Traits ◽  
And Behavior ◽  
Brain Behavior

Abstract All species, including humans, are exposed to endocrine-disrupting chemicals (EDCs). Previous experiments have shown behavioral deficits caused by EDCs that have implications for social competence and sexual selection. The neuromolecular mechanisms for these behavioral changes induced by EDCs have not been thoroughly explored. Here, we tested the hypothesis that EDCs administered to rats during a critical period of embryonic brain development would lead to the disruption of normal social preference behavior, and that this involves a network of underlying gene pathways in brain regions that regulate these behaviors. Rats were exposed prenatally to human-relevant concentrations of EDCs (polychlorinated biphenyls [PCBs], vinclozolin [VIN]), or vehicle. In adulthood, a sociosexual preference test was administered. We profiled gene expression of in preoptic area, medial amygdala, and ventromedial nucleus. Prenatal PCBs impaired sociosexual preference in both sexes, and VIN disrupted this behavior in males. Each brain region had unique sets of genes altered in a sex- and EDC-specific manner. The effects of EDCs on individual traits were typically small, but robust; EDC exposure changed the relationships between gene expression and behavior, a pattern we refer to as dis-integration and reconstitution. These findings underscore the effects that developmental exposure to EDCs can have on adult social behavior, highlight sex-specific and individual variation in responses, and provide a foundation for further work on the disruption of genes and behavior after prenatal exposure to EDCs.

scholarly journals Prenatal exposure to EDCs dis-integrates and reconstitutes neuromolecular-behavioral relationships in adult rats

2020 ◽  
Author(s):  
Morgan E. Hernandez Scudder ◽  
Rebecca L. Young ◽  
Lindsay M. Thompson ◽  
Pragati Kore ◽  
David Crews ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prenatal Exposure ◽  
Social Preference ◽  
Endocrine Disrupting Chemicals ◽  
Preference Test ◽  
Brain Regions ◽  
Mate Preference ◽  
Adult Rats ◽  
Preference Behavior ◽  
Opposite Sex

AbstractExposure to endocrine-disrupting chemicals (EDCs) is ubiquitous in all species, including humans. Previous studies have shown behavioral deficits caused by EDCs that have implications for social competence and sexual selection. The neuromolecular mechanisms for these behavioral changes induced by EDCs have not been thoroughly explored. Here, we tested the hypothesis that EDCs administered to rats during a critical period of embryonic brain development would lead to disruption of normal social preference behavior, and that this involves a network of underlying gene pathways in brain regions that regulate these behaviors. Rats were exposed prenatally to human-relevant concentrations of EDCs [polychlorinated biphenyls (PCB), an industrial chemical mixture; vinclozolin (VIN), a fungicide], or vehicle. In adulthood, a sociosexual preference test (choice between hormone-primed and hormone-depleted opposite-sex rats) was administered. We profiled gene expression of in three brain regions involved in these behaviors [preoptic area (POA), medial amygdala (MeA), ventromedial nucleus (VMN)]. Prenatal PCBs impaired sociosexual preference in both sexes, and VIN disrupted this behavior in males. Each brain region (POA, MeA, VMN) had unique sets of genes altered in a sex- and EDC-specific manner. Sexually dimorphic gene expression disruption was particularly prominent for gene modules pertaining to sex steroid hormones and nonapeptides in the MeA. EDC exposure also changed the relationships between gene expression and behavior in the mate preference test, a pattern we refer to as dis-integration and reconstitution. These findings underscore the profound effects that developmental exposure to EDCs can have on adult social behavior, highlight sex-specific and individual variation in responses, and provide a foundation for further work on the disruption of mate preference behavior after prenatal exposure to EDCs.

104 Epigenetic Changes Due to Environmental Toxicants: An Animal Health Concern

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 54-54
Author(s):  
Cheryl S Rosenfeld
Keyword(s):  
Human Health ◽  
Steroid Receptors ◽  
Animal Health ◽  
Endocrine Disrupting Chemicals ◽  
Brain Regions ◽  
The Body ◽  
Health Concern ◽  
Environmental Toxicants ◽  
Epigenetic Changes ◽  
Developmental Exposure

Abstract Endocrine disrupting chemicals (EDCs) mimic natural hormones in the body, but they are not subject to normal homeostatic regulatory mechanisms. One such EDC that is particularly important in animal and human health is bisphenol A (BPA) that is an industrial chemical used to harden plastic, and thus, it is prevalent in many common household items. Notably, BPA, and likely other EDCs, persist in the environment. Besides binding to steroid and non-steroid receptors, BPA and other EDCs may induce epigenetic changes directly or by affecting gut bacteria that can promote such host changes. The objective of current studies was to determine whether developmental exposure to BPA and/or genistein, a phytoestrogen, induce persistent epigenetic and transcriptomic changes in various brain regions and the placenta. Additionally, the ability of these chemicals to alter gut microbiota and gut metabolites that may trigger such epigenetic alterations were investigated. Animal models used to examine for such effects included California mice (Peromyscus californicus), deer mice (Peromyscus maniculatus), laboratory mice (Mus musculus), and eastern painted turtles (Chrysemys picta). To link these ‘omics changes to actual phenotypic modifications, several behavioral domains were assessed in these species following developmental exposure to these compounds. Results across taxa clearly show that BPA and genistein leads to behavioral deficits, including cognitive and social impairments, anxiogenic behaviors, and reduced voluntary physical activity. Correspondingly, both chemicals transformed the epigenome and transcriptome in key brain regions and the placenta. Gut dysbiosis and stimulation of harmful bacterial metabolites ensued following early EDC exposure, and such effects persisted through adulthood. By using a one health medicine approached that evaluated various vertebrate animal species, there is solid evidence that perinatal exposure to BPA and genistein reprograms the epigenome and thereby lead to longstanding health consequences. Such findings have important veterinary and human health ramifications.

scholarly journals Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiao Li ◽  
Jakob Seidlitz ◽  
John Suckling ◽  
Feiyang Fan ◽  
Gong-Jun Ji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Structural Changes ◽  
Brain Regions ◽  
Cell Type ◽  
Major Depressive ◽  
Structural Differences ◽  
Neuroimaging Data ◽  
Cell Type Specific

AbstractMajor depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.

scholarly journals Temporal changes in DNA methylation and RNA expression in a small song bird: within- and between-tissue comparisons

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Melanie Lindner ◽  
Irene Verhagen ◽  
Heidi M. Viitaniemi ◽  
Veronika N. Laine ◽  
Marcel E. Visser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Environmental Conditions ◽  
Brain Regions ◽  
Temporal Changes ◽  
Egg Laying ◽  
Gene Body ◽  
Cpg Site ◽  
Repeated Sampling ◽  
Over Time

Abstract Background DNA methylation is likely a key mechanism regulating changes in gene transcription in traits that show temporal fluctuations in response to environmental conditions. To understand the transcriptional role of DNA methylation we need simultaneous within-individual assessment of methylation changes and gene expression changes over time. Within-individual repeated sampling of tissues, which are essential for trait expression is, however, unfeasible (e.g. specific brain regions, liver and ovary for reproductive timing). Here, we explore to what extend between-individual changes in DNA methylation in a tissue accessible for repeated sampling (red blood cells (RBCs)) reflect such patterns in a tissue unavailable for repeated sampling (liver) and how these DNA methylation patterns are associated with gene expression in such inaccessible tissues (hypothalamus, ovary and liver). For this, 18 great tit (Parus major) females were sacrificed at three time points (n = 6 per time point) throughout the pre-laying and egg-laying period and their blood, hypothalamus, ovary and liver were sampled. Results We simultaneously assessed DNA methylation changes (via reduced representation bisulfite sequencing) and changes in gene expression (via RNA-seq and qPCR) over time. In general, we found a positive correlation between changes in CpG site methylation in RBCs and liver across timepoints. For CpG sites in close proximity to the transcription start site, an increase in RBC methylation over time was associated with a decrease in the expression of the associated gene in the ovary. In contrast, no such association with gene expression was found for CpG site methylation within the gene body or the 10 kb up- and downstream regions adjacent to the gene body. Conclusion Temporal changes in DNA methylation are largely tissue-general, indicating that changes in RBC methylation can reflect changes in DNA methylation in other, often less accessible, tissues such as the liver in our case. However, associations between temporal changes in DNA methylation with changes in gene expression are mostly tissue- and genomic location-dependent. The observation that temporal changes in DNA methylation within RBCs can relate to changes in gene expression in less accessible tissues is important for a better understanding of how environmental conditions shape traits that temporally change in expression in wild populations.

scholarly journals Evolutionary Patterns of Sex-Biased Genes in Three Species of Haplodiploid Insects

Insects ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 326
Author(s):  
Yu-Jun Wang ◽  
Hua-Ling Wang ◽  
Xiao-Wei Wang ◽  
Shu-Sheng Liu
Keyword(s):  
Gene Expression ◽  
Slow Rate ◽  
Species Complex ◽  
Evolutionary Patterns ◽  
Protein Coding ◽  
Coding Sequences ◽  
Species Comparisons ◽  
Differential Gene ◽  
Males And Females ◽  
And Behavior

Females and males often differ obviously in morphology and behavior, and the differences between sexes are the result of natural selection and/or sexual selection. To a great extent, the differences between the two sexes are the result of differential gene expression. In haplodiploid insects, this phenomenon is obvious, since males develop from unfertilized zygotes and females develop from fertilized zygotes. Whiteflies of the Bemisia tabaci species complex are typical haplodiploid insects, and some species of this complex are important pests of many crops worldwide. Here, we report the transcriptome profiles of males and females in three species of this whitefly complex. Between-species comparisons revealed that non-sex-biased genes display higher variation than male-biased or female-biased genes. Sex-biased genes evolve at a slow rate in protein coding sequences and gene expression and have a pattern of evolution that differs from those of social haplodiploid insects and diploid animals. Genes with high evolutionary rates are more related to non-sex-biased traits—such as nutrition, immune system, and detoxification—than to sex-biased traits, indicating that the evolution of protein coding sequences and gene expression has been mainly driven by non-sex-biased traits.

scholarly journals Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Angela M. Crist ◽  
Kelly M. Hinkle ◽  
Xue Wang ◽  
Christina M. Moloney ◽  
Billie J. Matchett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Digital Pathology ◽  
Selective Vulnerability ◽  
Brain Regions ◽  
Biochemical Analyses ◽  
The Brain ◽  
Relevant Gene ◽  
Tau Expression

AbstractSelective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.

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