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Posted Monday November, 16th 2020

A Comprehensive Overview on Stress Neurobiology: Basic Concepts and Clinical Implications

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Stress is recognized as an important issue in basic and clinical neuroscience research, based upon the founding historical studies by Walter Canon and Hans Selye in the past century, when the concept of stress emerged in a biological and adaptive perspective. A lot of research after that period has expanded the knowledge in the stress field. Since then, it was discovered that the response to stressful stimuli is elaborated and triggered by the, now known, stress system, which integrates a wide diversity of brain structures that, collectively, are able to detect events and interpret them as real or potential threats. However, different types of stressors engage different brain networks, requiring a fine-tuned functional neuroanatomical processing. This integration of information from the stressor itself may result in a rapid activation of the Sympathetic-Adreno-Medullar (SAM) axis and the Hypothalamus-Pituitary-Adrenal (HPA) axis, the two major components involved in the stress response. The complexity of the stress response is not restricted to neuroanatomy or to SAM and HPA axes mediators, but also diverge according to timing and duration of stressor exposure, as well as its short- and/or long-term consequences. The identification of neuronal circuits of stress, as well as their interaction with mediator molecules over time is critical, not only for understanding the physiological stress responses, but also to understand their implications on mental health.

Introduction

Stress is recognized as an important issue in basic and clinical neuroscience research (de Kloet et al., 2005a; McEwen et al., 2015). Although this physiological phenomenon is fundamental to survival, it is also strongly related to several brain disorders including, depression, anxiety, post-traumatic stress disorder (Ruiz et al., 2007; Heim et al., 2008; Martin et al., 2009; Walsh, 2011; Saveanu and Nemeroff, 2012; Nemeroff, 2016) accordingly to the International Classification of Diseases, 10th edition (ICD-10). Research focusing on the complexity of stress is still challenging, but several studies in animals and humans have made substantial contributions to its progress in recent years, as reviewed by Hariri and Holmes (2015). However, it is crucial to provide more meaningful advances in the stress field by means of a translational approach, integrating basic knowledge and clinical practice.

In this review article, we briefly describe the history of stress research and highlight stress basic concepts, explore the complex neuroanatomy, in fact networks, of the stress system and its keen axes and mediators, as well as the time domains of the stress response. Lastly, we raise clinical implications from these concepts and discuss future research challenges on the stress field.

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