Neuroendocrine Response to Psychosocial Stressors, Inflammation Mediators and Brain-Periphery Pathways of Adaptation

Threats, challenging events, adverse experiences, predictable or unpredictable, namely stressors, characterize life, being unavoidable for humans. The hypothalamus-pituitary-adrenal axis (HPA) and the sympathetic nervous system (SNS) are well-known to underlie the physiology of adaptation to psychosocial stress, in the context of a variety of other interacting systems, signals and mediators. However, considerable effort is still required to fully elucidate such modulatory cues in order to understand how and why the 'brain-body axis' acts for resilience or, on the contrary, cannot cope with stress, under a biochemical and biological point of view. Indeed, failure to adapt increases both the risk of developing and/or relapsing into mental illnesses such as burnout, post-traumatic stress disorder (PTSD) and at least some types of depression, even favoring/worsening the onset of neurodegenerative and somatic co-morbidities, especially in the elderly. We will review here current knowledge on this area, focusing on works presenting the main brain centers responsible of stressor interpretation and processing, as well as on those highlighting the physiology/biochemistry of the ensuing endogenous responses, trying to evidence the most promising lines of future research. Autonomic and HPA patterns, inflammatory cascades and energy/redox metabolic arrays will be presented, on the one hand, as promoters of allostasis, leading towards adaptation to psychosocial stress and homeostasis, on the other as possible vulnerability factors for allostatic overload and non-adaptive reactions. The existence of allostasis buffering systems will be also underscored. Finally, we will prospect that the combined uses of cell cultures, animal models and wide-omics investigations may constitute a powerful tool to entangle the biochemical signature of resilience or stress-related illness, a much helpful facet for improving patients' treatment and monitoring