Chronic social instability stress differentially affects the behavior and the transcriptome of the anterodorsal bed nucleus of the stria terminalis between male and female mice

Stress can be broken down into systemic and processive stressors with processive stressors requiring higher limbic processing. These are also often called social stressors as they require an understanding of social dynamics as opposed to physical based stressors. This differing of processing necessitates we study both phenomena. Additionally, sex is an important aspect of stress research as men and women show differing responses to stress and mood disorder development. To study this, we used a chronic social instability stress (CSIS) paradigm to stress male and female mice. This paradigm is approximately 7-weeks long and involves changing the cage mates of a mouse every 3 days so stable social dynamics cannot form. Afterwards, one cohort was used for avoidance behavior testing using the open field test, the elevated plus maze, the light/dark box emergence test, and the novelty suppressed feeding test. A second cohort was used for bulk RNA-Sequencing of the anterodorsal bed nucleus of the stria terminalis which is a limbic structure known to be related to chronic stress signaling. In the behavior assays, CSIS caused the females to be less avoidant, while the males became more avoidant. Additionally, we found that a low estrogen state in the females caused them to be less avoidant than in a high estrogen state. In the transcriptome, we found major differences between the males and females with the males expressing more genes related to transcription whereas the females expressed more genes related to synaptic transmission. We also found that the transcriptome in the males is more sensitive to the stress than the females. In summary, we have found how social stress is differentially regulated between males and females and how this may be related to the development of stress-related behavioral changes.