Journal of Translational Neurosciences

Description

The skin, like few other organs, is constantly stressed by both external and internal factors. The effect that psychological stress has on the physiology and pathology of the skin is added on top of this. The brain–skin connection, which may be at the root of stress-induced or exacerbated inflammatory skin diseases, is examined in this paper, along with pertinent general principles of skin neuroimmunology and neuroendocrinology. In particular, we depict the skin and its appendages as both a potent source of these typical Immunomodulatory stress response mediators and a prominent target of key stress mediators like corticotropin-releasing hormone, ACTH, cortisol, catecholamines, prolactin, substance P, and nerve growth factor. The skin has developed a fully functional peripheral equivalent of the skin hypothalamic–pituitary–adrenal axis as an independent, local stress response system, and we discuss the available were evidence that this system has been established. Melatonin, probably the most potent neuroendocrine antioxidant, is also expressed by the skin and hair follicles in response to stress-induced oxidative damage.

Impact on the Immune System in Sophisticated Experiments with Hypophysectomized Rats

 The identification of promising molecular targets for therapeutic stress intervention and the cross-talk between peripheral and systemic responses to psychological stress are two major unmet challenges in cutaneous stress research that we lastly outline. Psychological stress is a common occurrence in life, usually brought on by a stimulus stressor that causes the brain to respond with stress perception. The immune, endocrine, and nervous systems, among other physiological systems, are then activated in the body stress response. The hypothesis proposed by Walter Cannon states that the stress response is a psychophysiological survival mechanism that evolved through evolution. It enables an individual to fight or flight in response to acute stress, such as a predator, and to conserve energy in response to chronic stress. However, stressors have changed, and the current meaning of stress does not include the individual's ability to fight or evade predators or conserve energy for survival. As a result, pathophysiological changes caused by stress are misdirected and contribute to the progression of a wide range of diseases, including autoimmune, inflammatory, and allergic conditions. The hypothalamic–pituitary–adrenal axis is activated when psychological stress is perceived, resulting in the release of prolactin (PRL), Corticotropin-Releasing Hormone (CRH), and Adrenal Cortisol (ACTH). The dorsal root ganglia also show an upregulation of substance P (SP) and Calcitonin Gene-Related Peptide (CGRP). The local production of CRH, ACTH, and Glucocorticoids (GCs), as well as the release of inflammatory cytokines and the sprouting of SP+ nerve fibers, may be translated into a skin stress response. Mast cells play a central role in the skin's response to stress because they are targets for stress-triggered factors and effector cells that play a role in things like neurogenic skin inflammation. A skin stress response can also be triggered by environmental factors, which may be transmitted to the brain, where it affects behavior and increases vulnerability to additional stress perception. Nerve growth factor or NGF. Additional pituitary hormones, like Prolactin (PRL), have been shown to have an impact on the immune system in sophisticated experiments with hypophysectomized rats. In these studies, the absence of PRL caused immune system abnormalities, such as increased thymic atrophy and lymphopenia that could be reversed with syngeneic pituitary grafting. Intriguingly, elevated PRL inhibits apoptosis in thymocytes exposed to glucocorticoids in vivo. This suggests that elevated PRL functions physiologically to maintain T lymphocyte survival and function in situations of elevated glucocorticoids, such as stress. In addition to the stress-triggered activation of the HPA axis, neurohormonal responses to stress also include an increase in catecholamines and activation of the sympathetic nervous system. This phenomenon has received much less attention than the stress-triggered activation of the HPA axis. It has been known for half a century that lymphoid organs are heavily innervated by noradrenergic nerve fibers. Since then, more and more evidence suggests that catecholamines and the sympathetic nervous system regulate the immune system at the regional, local, and systemic levels.

Proximal and Distal Mediators in the Stress Response's Hierarchy of Factors

Adrenergic receptors are expressed by lymphocytes, and they respond to catecholamine stimulation by undergoing distinct changes in lymphocyte trafficking, circulation, proliferation, and cytokine production in response to stress-induced lymphocytosis. Probably in order to coordinate peripheral responses to stress and maintain cutaneous and global homeostasis, the skin has its own neuroendocrine system that is tightly linked to systemic neuroendocrine axes. Human mapping of the cutaneous CRH signaling system revealed that the CRH Receptor Type 1 (CRH-R1) is expressed in all major cellular populations of the epidermis, dermis, and subcutis. The CRH-R2 gene is only expressed in the dermis and adnexal structures, and it appears that CRH-R1 is the most common isoform of CRH-R. The CRH-R2 protein and gene are abundantly expressed across all cutaneous regions in mouse skin. In conclusion, there is now solid evidence for the existence of a defined brain–skin axis and an intrafollicular HPA axis whose modulation by chronic psychological stress is of profound dermatological interest. A new era in neuroimmunology must begin, and clearly the primary objective is to distinguish between proximal and distal mediators in the stress response's hierarchy of factors. This can only be accomplished through interdisciplinary research and integrative approaches. Last but not least, dermatologists should pay much more attention to how psychological stress affects skin disorders. This is not only for the benefit of their patients but also because the skin is a very clinically relevant model system for studying the neuroimmunology of central and peripheral stress responses.