Abstract Body

Social interactions are an integral part of our lives, forming the fundamental basis of social hierarchy. Social interactions may be both beneficial and harmful, being a major source of triggers of stressful conditions. Failure to cope with these conditions, which manifest in the form of social stress, may induce the development of chronic inflammation and stress-related diseases. The hereditary nature of social rank has enabled us to develop a selectively bred mouse model, which represents the stable internal states of dominance and submissiveness. An increasing amount of our data demonstrates that dominant (Dom) and submissive (Sub) mice exhibit stress resilience and vulnerability respectively. The dissimilar innate stress sensitivity of Dom and Sub mice is demonstrated by differential: a) responses to psychotropic agents; b) patterns of short-term and long-term synaptic plasticity; c) compositions of the gut microbiome and d) inflammatory profile. It has also been discovered that Sub mice exhibit markedly shorter lifespans, accompanied by age-dependent splenomegaly, in comparison to Dom mice. Our most recent data demonstrates that innate stress sensitivity of Sub mice is associated with their increased immune reactivity. It was hence found that Sub nulliparous females show an exacerbated cytokine response to viral mimetic Poly(I:C) when compared to Dom females. Furthermore, we have found that the baseline response of Sub mice to the non-competitive NMDA receptor antagonist MK-801, was substantially higher than that of Dom mice, this effect being further potentiated by prenatal Poly(I:C) exposure. Our findings suggest that inherited stress sensitivity may lead to inflammation-driven functional and physiological changes. In view of the current Covid-19 viral pandemic it is of utmost importance to determine the role of viral infection induced maternal immune activation which significantly affects pregnant women and may have a long-lasting and diverse impact on future generations.