Current concepts of the etiology of stress-related conditions including anxiety and post-traumatic stress disorders emphasize the critical contribution of social stress, which is ubiquitous in modern human societies overwhelmed with abundant interpersonal contact in real-life as well as via social media. Research focused on the causes and consequences of social isolation stress indicates that social interactions are key to mental and physical well-being in humans and many animals including rodents. On the other hand, there is mounting evidence that harmful and uncontrollable social partners can be extremely detrimental to physical and mental health. The aim of this panel will be to present recent advances in understanding the translational mechanisms underlying the ambiguous nature of social interactions and to define a novel concept of social homeostasis. The symposium will highlight current perspectives from both basic animal and human research by targeting limbic dysfunction, oxytocin system alterations, and neuroinflammatory abnormalities in social isolation stress, social defeat stress, and patients with clinically established anxiety and post-traumatic stress disorders. Specifically, Rene Hurlemann (RH) will present recent functional MRI (fMRI) studies showing that chronic social isolation stress is associated with aberrant limbic responses to social trust and fear signals. Valery Grinevich (VG) will demonstrate morphological and electrophysiological alterations in oxytocin neurons of adult rats caused by acute social isolation stress. Ulrike Schmidt (US) will present molecular and clinical data on the function and regulation of oxytocin signaling in traumatized individuals and various animal models of stress. Anne-Kathrin Gellner (AKG) will link social defeat stress to distinct neuroinflammatory pathways including peripheral and central inflammasome signaling.
Social stress response shaped by inflammation: from molecule to behavior and back
Anne-Kathrin Gellner, Bonn (Germany)
Chronic stress contributes to neuropsychiatric disorders like depression and anxiety. Especially social stress is inevitably in modern human societies overwhelmed with constant interpersonal interaction in real-life and on social media. Moreover, chronic stress affects not only mental health but has been shown to alter the whole organism including immune and endocrine responses. Stress-vulnerability varies in humans and animals, meaning that the same stress load can affect the individuals differently leading to susceptible and resilient phenotypes. Factors of stress resilience are of immense interest for understanding the cause but also treatment of neuropsychiatric disorders. Intact NLRP3 inflammasome signaling was previously demonstrated to be a prerequisite for the development of depressive behaviors after chronic non-social stressors. The relevance of the NLRP3 inflammasome in a translationally important social stress models is still unknown.
Therefore, we first used NLRP3-KO and WT mice and exposed them to a chronic social defeat stress model. Here, we could show that disrupted NLRP3-signalling prevents the development of stress-induced affective symptoms, learning impairments, and signs of immune response mimicking inflammatory patterns usually seen in infectious disease. We next explored whether both systemic and central nervous inflammation together or independently contribute to this phenotype by pharmacological NLRP3 inhibition and found a complex modulation of the stress response on the behavioral, cellular, and molecular level. Our work highlights the role of the innate immune system in stress resilience and social stress-induced neuroinflammation, suggesting it as a pharmacological target in neuropsychiatric disorders.