Hypothalamic transcriptome of tame and aggressive silver foxes (Vulpes vulpes) identifies gene expression differences shared across brain regions.

The underlying neurological events accompanying dog domestication remain elusive. To reconstruct the domestication process in an experimental setting, silver foxes (Vulpes vulpes) have been deliberately bred for tame vs aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. The hypothalamus is an essential part of the hypothalamic-pituitary-adrenal axis and regulates the fight-or-flight response, and thus, we hypothesized that selective breeding for tameness/aggressiveness has shaped the hypothalamic transcriptomic profile. RNA-seq analysis identified 70 differentially expressed genes (DEGs). Seven of these genes, DKKL1, FBLN7, NPL, PRIMPOL, PTGRN, SHCBP1L and SKIV2L, showed the same direction expression differences in the hypothalamus, basal forebrain and prefrontal cortex. The genes differentially expressed across the three tissues are involved in cell division, differentiation, adhesion and carbohydrate processing, suggesting an association of these processes with selective breeding. Additionally, 159 transcripts from the hypothalamus demonstrated differences in the abundance of alternative spliced forms between the tame and aggressive foxes. Weighted gene coexpression network analyses also suggested that gene modules in hypothalamus were significantly associated with tame vs aggressive behavior. Pathways associated with these modules include signal transduction, interleukin signaling, cytokine-cytokine receptor interaction and peptide ligand-binding receptors (eg, G-protein coupled receptor [GPCR] ligand binding). Current studies show the selection for tameness vs aggressiveness in foxes is associated with unique hypothalamic gene profiles partly shared with other brain regions and highlight DEGs involved in biological processes such as development, differentiation and immunological responses. The role of these processes in fox and dog domestication remains to be determined.

Aggressive behavior and stress response after oxytocin administration in male Norway rats selected for different attitudes to humans.

Oxytocin (OXT) is known to influence on social behaviors, including intermale aggression and hypothalamic-pituitary-adrenal (HPA) axis activity. However, there are no data on the effects of oxytocin on intermale aggression and HPA axis activity in rats selected for elimination and enhancement of aggressiveness towards humans. The aim of this study is to elucidate the role of oxytocin in expression of aggressive behavior and stress response in Norway rats selected for elimination (tame) and enhancement (aggressive) of an aggressive-defensive reaction to humans. Oxytocin was administered to males via nasal applications once or for 5 days (daily). Resident-intruder test showed that in aggressive males, single oxytocin administration caused an increase in the latent period of aggressive interactions and a decrease in the percentage of direct aggression time (not including the time of lateral threat postures) as compared to the control aggressive rats administered with saline. After a 5-day oxytocin administration, aggressive animals demonstrated shorter time of aggressive interactions compared to the control rats. Resident-intruder test revealed no significant changes in behavior of tame rats after single oxytocin administration, while multiple administration caused an increase in aggressive behavior in tame rats. Oxytocin applications caused an elevation of corticosterone level after restriction in aggressive males, but did not affect expression of Crh, Crh1 and Crhr2 genes in hypothalamus in either tame or aggressive rats. The data obtained indicate significant role of oxytocinergic system in the behavior formed in the process of selection by reaction to humans.

Conserved methylation of the glucocorticoid receptor gene exon 1(7) promoter in rats subjected to a maternal methyl-supplemented diet.

It is well known that the early life experiences affect stress responses and other physiological and behavioral traits in adulthood. Both rat and human studies have shown that early postnatal effects are associated with methylation of the hippocampal glucocorticoid receptor gene exon 1(7) (rat) and 1-F (human) promoters. Methylation of these sites is also seen following methionine administration in adult rats. However, it remains unclear whether similar alterations in DNA methylation profiles can result from prenatal influences. To address this question, we fed pregnant rats a methyl-supplemented diet that resulted in alteration of the stress response. However, methylation analysis revealed no effect of methyl supplements on methylation patterns of the glucocorticoid receptor gene exon 1(7) promoter in offspring. These results suggest that the pre- and postnatal effects of methyl supplementation have different mechanisms.