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Cell-type and sex-specific rhythmic gene expression in the nucleus accumbens

ABSTRACT: Cell-type and sex-specific rhythmic gene expression in the nucleus accumbens

PROVIDER: PRJNA1106620 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28856900.fastq.gz	Fastqsanger.gz
	SRR28856901.fastq.gz	Fastqsanger.gz
	SRR28856902.fastq.gz	Fastqsanger.gz
	SRR28856903.fastq.gz	Fastqsanger.gz
	SRR28856904.fastq.gz	Fastqsanger.gz

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Cell-type and sex-specific rhythmic gene expression in the nucleus accumbens

Project description:Circadian rhythms are critical for human health and are highly conserved across species. Disruptions in these rhythms contribute to many diseases, including psychiatric disorders. Previous results suggest that circadian genes modulate behavior through specific cell types in the nucleus accumbens (NAc), particularly dopamine D1-expressing medium spiny neurons (MSNs). However, diurnal rhythms in transcript expression have not been investigated in NAc MSNs. In this study we identified and characterized rhythmic transcripts in D1- and D2-expressing neurons and compared rhythmicity results to homogenate as well as astrocyte samples taken from the NAc of male and female mice. We find that all cell types have transcripts with diurnal rhythms and that top rhythmic transcripts are largely core clock genes, which peak at approximately the same time of day in each cell type and sex. While clock-controlled rhythmic transcripts are enriched for protein regulation pathways across cell type, cell signaling and signal transduction related processes are most commonly enriched in MSNs. In contrast to core clock genes, these clock-controlled rhythmic transcripts tend to reach their peak in expression about 2 hours later in females than males, suggesting diurnal rhythms in reward may be delayed in females. We also find sex differences in pathway enrichment for rhythmic transcripts peaking at different times of day. Protein folding and immune responses are enriched in transcripts that peak in the dark phase, while metabolic processes are primarily enriched in transcripts that peak in the light phase. Importantly, we also find that several classic markers used to categorize MSNs are rhythmic in the NAc. This is critical since the use of rhythmic markers could lead to over- or under-enrichment of targeted cell types depending on the time at which they are sampled. This study greatly expands our knowledge of how individual cell types contribute to rhythms in the NAc.

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Integrative analysis of sex-specific microRNA networks following stress in mouse nucleus accumbens

Project description:Adult women are twice as likely as men to suffer from affective and anxiety disorders, although the mechanisms underlying heightened female stress susceptibility are incompletely understood. Recent findings in mouse Nucleus Accumbens (NAc) suggest a role for DNA methyltransferase-driven sex differences in genome-wide transcriptional profiles. However, the role of another epigenetic process—microRNA (miR) regulation—has yet to be explored. We exposed male and female mice to Subchronic Variable Stress (SCVS), a stress paradigm that produces depression-like behavior in female, but not male, mice, and performed next-generation mRNA and miR sequencing on NAc tissue. We applied a combination of differential expression, miR-mRNA network and functional enrichment analyses to characterize the transcriptional and post-transcriptional landscape of sex differences in NAc stress response. We find that male and female mice exhibit largely non-overlapping miR and mRNA profiles following SCVS. The two sexes also show enrichment of different molecular pathways and functions. Collectively, our results suggest that males and females mount fundamentally different transcriptional and post-transcriptional responses to SCVS and engage sex-specific molecular processes following stress. These findings have implications for the pathophysiology and treatment of stress-related disorders in women.

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Adult male prairie vole nucleus accumbens RNAseq dataset for "Prolonged partner separation erodes nucleus accumbens transcriptional signatures of pair bonding in male prairie voles."

Project description:This dataset contains RNA sequencing results from adult male prairie voles that were in either opposite-sex or same-sex pairs that were subsequently either separated from or remained paired with their partner for either 48 hours or 4 weeks prior to collecting nucleus accumbens tissue. The goal of this experiment was to determine the nucleus accumbens transcriptional response specific to separation from an opposite-sex partner. RNA sequencing was done on polyA enriched transcripts using Illumina single-end sequencing. Samples from 3 groups were from a Ribo-seq protocol using a virally delievered, vole optimized Translating Ribosome Affinity Purification construct (Heiman et al., 2008). These samples contain files for both the input fraction and the pulldown fraction (denoted with a _P suffix).

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Project description:We have aimed to analyze dexamethasone-induced transcriptional profiling in astrocytes and neurons of the mouse nucleus accumbens (NAc).

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Project description:Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability. mRNA profiles of sex-specific in stress response were generated in the Nucleus Accumbens for 3 female control mice, 3 male control mice, 3 stressed female mice, 3 stressed male mice. Cre-mediated Dnmt3a knock-out was performed on stressed mice, with 3 males and 3 females expressing control GFP and 3 males and 3 females expressing CRE/GFP.

2016-08-04 | E-GEOD-85136 | biostudies-arrayexpress

Transcriptomics in the nucleus accumbens shell reveal sex- and reinforcer-specific signatures associated with morphine and sucrose craving

Project description:RNA-sequencing was performed using nucleus accumbens tissue from male and female rats following 1 or 30 days of morphine self-admininstration or sucrose self-adminnistration.

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Single nucleus RNA-seq of rat nucleus accumbens

Project description:Single nucleus RNA-seq of nucleus accumbens from male Brown Norway rats after a single acute or repeated saline injections

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Sex differences in the ventral tegmental area and nucleus accumbens proteome at baseline and following nicotine exposure

Project description:Sex differences in behaviors relevant to nicotine addiction have been observed in rodent models and human subjects. Behavioral, imaging and epidemiological studies also suggest underlying sex differences in mesolimbic dopamine signaling pathways. In this study we evaluated the proteome in the ventral tegmental area (VTA) and nucleus accumbens (NAc) shell in male and female mice. Experimental groups included two mouse strains (C3H/HeJ and C57BL/6J) at baseline, a sub-chronic, rewarding regimen of nicotine in C3H/HeJ mice, and chronic nicotine administration and withdrawal in C57BL/6J mice. Isobaric labeling with a TMT 10-plex system, sample fractionation, and tandem mass spectrometry were used to quantify changes in protein abundance. Similar or greater numbers of differentially regulated proteins were found between sexes at baseline in C3H/HeJ or C57BL/6J mice than within sexes following their respective regimen of nicotine administration. Despite differences by sex, strain, and nicotine exposure parameters, glial fibrillary acidic protein (GFAP) and dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32, Ppp1r1b) were repeatedly identified as significantly altered proteins, especially in the VTA. Further, network analyses showed sex- and nicotine-dependent regulation of a number of signaling pathways, including dopaminergic signaling. Sub-chronic nicotine exposure in female mice increased proteins related to dopaminergic signaling in the NAc shell but decreased them in the VTA, whereas the opposite pattern was observed in male mice. In contrast, dopaminergic signaling pathways were similarly upregulated in both male and female VTA after chronic nicotine and withdrawal. Overall, this study identifies significant sex differences in the proteome of the mesolimbic system, at baseline and after nicotine reward or withdrawal, which may help explain differential trajectories and susceptibility to nicotine addiction in males and females.

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Project description:Cell-type specific regulation mechanisms of depression in the nucleus accumbens

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Estrogen-dependent up-regulation of Adcyap1r1 expression in nucleus accumbens is associated with genetic predisposition of sex-specific QTL for alcohol consumption on rat chromosome 4

Project description:RNA-seq was performed on the nucleus accumbens of female (F) interval-specific congenic strain-B (P.NP-ISCS-B) and inbred alcohol preferring (iP) control rat

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