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

[ Vol. 21 , Issue. 1 ]


Lionella Palego, Gino Giannaccini and Laura Betti*   Pages 2 - 19 ( 18 )


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 adaptation to psychosocial stress in the context of other interacting systems, signals and mediators. However, much more effort is necessary to elucidate these modulatory cues for a better understanding of how and why the "brain-body axis" acts for resilience or, on the contrary, cannot cope with stress from a biochemical and biological point of view. Indeed, failure to adapt increases the risk of developing and/or relapsing mental illnesses such as burnout, post-traumatic stress disorder (PTSD), and at least some types of depression, even favoring/worsening neurodegenerative and somatic comorbidities, especially in the elderly.

We will review here the current knowledge on this area, focusing on works presenting the main brain centers responsible for stressor interpretation and processing, together with those underscoring the physiology/biochemistry of endogenous stress responses. Autonomic and HPA patterns, inflammatory cascades and energy/redox metabolic arrays will be presented as allostasis promoters, leading towards adaptation to psychosocial stress and homeostasis, but also as possible vulnerability factors for allostatic overload and non-adaptive reactions. Besides, the existence of allostasis buffering systems will be treated. Finally, we will suggest promising lines of future research, particularly the use of animal and cell culture models together with human studies by means of high-throughput multi-omics technologies, which could entangle the biochemical signature of resilience or stress-related illness, a considerably helpful facet for improving patients’ treatment and monitoring.


Stressors, psychosocial stressors, neuroendocrine axis, inflammatory/redox patterns, stress coping, resilience, stress-related illness.


Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Department of Pharmacy, University of Pisa, Pisa, Department of Pharmacy, University of Pisa, Pisa

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