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.

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 EDCs Impair Mate and Odor Preference and Activation of the VMN in Male and Female Rats

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Morgan E Hernandez Scudder ◽  
Amy Weinberg ◽  
Lindsay Thompson ◽  
David Crews ◽  
Andrea C Gore
Keyword(s):  
Preference Test ◽  
Brain Regions ◽  
Female Rats ◽  
Early Gene ◽  
Odor Preference ◽  
Pregnant Rat ◽  
Discrimination Ability ◽  
Preference Behavior ◽  
Male And Female Rats ◽  
Aroclor 1221

Abstract Environmental endocrine-disrupting chemicals (EDCs) disrupt hormone-dependent biological processes. We examined how prenatal exposure to EDCs act in a sex-specific manner to disrupt social and olfactory behaviors in adulthood and underlying neurobiological mechanisms. Pregnant rat dams were injected daily from embryonic day 8 to 18 with 1 mg/kg Aroclor 1221 (A1221), 1 mg/kg vinclozolin, or the vehicle (6% DMSO in sesame oil). A1221 is a mixture of polychlorinated biphenyls (weakly estrogenic) while vinclozolin is a fungicide (anti-androgenic). Adult male offspring exposed to A1221 or vinclozolin, and females exposed to A1221, had impaired mate preference behavior when given a choice between 2 opposite-sex rats that differed by hormone status. A similar pattern of impairment was observed in an odor preference test for urine-soaked filter paper from the same rat groups. A habituation/dishabituation test revealed that all rats had normal odor discrimination ability. Because of the importance of the ventrolateral portion of the ventromedial nucleus (VMNvl) in mate choice, expression of the immediate early gene product Fos was measured, along with its co-expression in estrogen receptor alpha (ERα) cells. A1221 females with impaired mate and odor preference behavior also had increased neuronal activation in the VMNvl, although not specific to ERα-expressing neurons. Interestingly, males exposed to EDCs had normal Fos expression in this region, suggesting that other neurons and/or brain regions mediate these effects. The high conservation of hormonal, olfactory, and behavioral traits necessary for reproductive success means that EDC contamination and its ability to alter these traits has widespread effects on wildlife and humans.

scholarly journals Localizing Brain Regions Associated with Female Mate Preference Behavior in a Swordtail

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e50355 ◽  
Author(s):  
Ryan Y. Wong ◽  
Mary E. Ramsey ◽  
Molly E. Cummings
Keyword(s):  
Brain Regions ◽  
Mate Preference ◽  
Female Mate Preference ◽  
Female Mate ◽  
Preference Behavior

scholarly journals Prenatal exposure to di-n-butyl phthalate induces erectile dysfunction in male adult rats

2021 ◽  
Vol 219 ◽  
pp. 112323
Author(s):  
Xiang Zhou ◽  
Tongtong Zhang ◽  
Lebin Song ◽  
Yichun Wang ◽  
Qijie Zhang ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Prenatal Exposure ◽  
Adult Rats ◽  
Male Adult ◽  
Butyl Phthalate

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 Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hui Li ◽  
Jing-An Chen ◽  
Qian-Zhi Ding ◽  
Guan-Yi Lu ◽  
Ning Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Histone Acetylation ◽  
Differentially Expressed Genes ◽  
Behavioral Sensitization ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Adult Rats ◽  
Mrna Microarray ◽  
H3 Acetylation

Abstract Background Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats. Methods We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays. Results In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 genes were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure. Conclusions The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.

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.

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