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Brain region and sex specific transcriptome of peripubertal stress induced adult male mice showing escalated aggression and adult female mice with no signs of aggression.

ABSTRACT: Purpose: The goal of this study is to uncover the molecular basis of peripubertal stress induced aggressive behaviour and its sex differences focussing on brain region specific transcriptome profiling (RNA-seq) and validation by quantitative reverse transcription polymerase chain reaction (qRT–PCR) Methods: Hypothalamus (Hypo) and Prefrontal cortex (PFC) mRNA profiles of 90-day-old control adult male and female and PPS exposed escalated aggressive adult male (SEagg) mice and non aggressive adult female (SNagg) were sequenced on Illumina HiSeq 2500, in 3 biological replicates.The FASTQ sequencing reads were adapter-trimmed along with a minimum length cut-off of 50 bases using Prinseq-lite. The reads were aligned to mouse genome assembly using TopHat (v.2.0.11) followed by reference-based assembly using Cufflinks (v.2.2.1). Then differentially expressing transcripts were identified using Cuffdiff (v.2.2.1). qRT–PCR validation was performed using SYBR Green assays. Results:Hypo of SEagg males showed 49 differentially expressed genes (DEGs) amongst which 28 were down-regulated, 20 were up-regulated and 1 was expressed in SEagg males but not in control males. PFC of SEagg males showed 87 DEGs amongst which 57 were downregulated, 28 were upregulated and 2 were only expressed in SEagg males but not control males. SNagg females showed 684 DEGs in Hypo and 152 DEGs in PFC when compared to their respective control samples. Conclusions: We provide the first prefrontal cortex and hypothalamus specific transcriptome profiles of peripubertal stress (PPS) exposed, Balb/c adult male mice exhibiting escalated aggression and Balb/c adult female mice showing no signs of aggression.

ORGANISM(S): Mus musculus

PROVIDER: GSE199844 | GEO | 2022/11/02

REPOSITORIES: GEO

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Project description:Animal and human studies suggest that inflammation is associated with behavioral disorders including aggression. We have recently shown that physical aggression of boys during childhood is strongly associated with reduced plasma levels of cytokines IL-1a, IL-4, IL-6, IL-8 and IL-10, later in early adulthood (Provencal et al., unpublished data). This study tests the hypothesis that there is an association between differential DNA methylation regions in cytokine genes in T cells and monocytes DNA in adult subjects and a trajectory of physical aggression from childhood to adolescence. We compared the methylation profiles of the entire genomic loci encompassing the IL-1a, IL-6, IL-4, IL10 and IL8 and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6 genes in adult males on a chronic physical aggression trajectory (CPA) and males with the same background who followed a normal physical aggression trajectory (control group). We used the method of methylated DNA immunoprecipitation (MeDIP) with comprehensive cytokine gene loci and TF loci microarray hybridization, statistical analysis and false discovery rate correction. We recruited two groups of Caucasian males who were born in families with a low socioeconomic status and were living at the time of the present study within 200km from our laboratory. The first group, composed of 8 subjects, had a history of chronic physical aggression from age 6 to 15 years (chronic physical aggression group, CPA). The second group, composed of 12 subjects, was recruited from the same longitudinal studies but included only those who did not have a history of chronic physical aggression from age 6 to 15 (Control group, CG). Using custom-designed microarrays with 44K probes tiling cytokines IL-1a, IL-6, IL-4, IL10 and IL8 and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6, we obtained DNA methylation profiles by meDIP-chip. Each profile was generated in triplicate.

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Brain region and sex specific transcriptome of peripubertal stress induced adult male mice showing escalated aggression and adult female mice with no signs of aggression.

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