Article

Effect of high population density environment on skin barrier function in mice

Authors:
  • Septem-Soken, Japan, Osaka
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Abstract

Previous reports have demonstrated that stressful stimuli markedly influenced physiological conditions and homeostasis. In this study, we examined the influence of high population density environment on barrier function and water retention property of skin in mice. Overcrowding stress induced dramatic body weight reduction and significant increase in adrenal gland weight. Macroscopic skin appearance showed moderate exfoliation and slight wrinkle formation in the stress group. Moreover epidermis hyperplasia not concomitant with inflammatory reactions such as infiltration of immunocytes and vasodilation was observed in the skin from the stress group. Skin surface conductance in the stress group was significantly lower than in the control group. On the other hand, transepidermal water loss in the stress group increased significantly, compared to the control group. Moreover, transdermal penetration of indomethacin and nicotinic acid amide was enhanced significantly. These results suggest that overcrowding stress induced impairment of barrier function and water retention property. To elucidate the mechanism of overcrowding stress-induce dry skin, contents of ceramide and pyrrolidone carboxylic acid, which are the important compounds contributing to those functions were evaluated. Both of them in stratum corneum declined significantly in the stress group. Taken together, these results demonstrate that overcrowding stress induced dry skin, and that the impairment of barrier function and water retention property correlated with decrease in ceramide and pyrrolidone carboxylic acid.

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... The degree of skin hydration can also affect the production of collagen and elastin, the skin regeneration process, and homeostasis maintenance [24][25][26][27]. The skin with a physiological amount of water is a barrier to microorganisms and external factors and can naturally exfoliate the epidermis [28][29][30][31][32]. The proper state and reactivity of the skin are related to Considering its action, diclofenac can be used in degenerative joint disease, longterm inflammations, such as spondylitis, painful menstruation, and after surgery [5][6][7]. ...
... The degree of skin hydration can also affect the production of collagen and elastin, the skin regeneration process, and homeostasis maintenance [24][25][26][27]. The skin with a physiological amount of water is a barrier to microorganisms and external factors and can naturally exfoliate the epidermis [28][29][30][31][32]. The proper state and reactivity of the skin are related to its homeostasis in the transport of water and ions within the cells of the skin tissue [17,23]. ...
... The skin, the body's largest organ, is the body's primary barrier protecting against various factors, i.e., UV radiation, mechanical injuries, pathogens, and xenobiotics [17,[26][27][28]30,31]. Through to its diversity, the skin is well adapted to perform different functions depending on its location. ...
Article
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Diclofenac belongs to the non-steroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory effects. Diclofenac administration on the skin may be associated with the appearance of side effects. The study aimed to evaluate the impact of diclofenac gel on transepithelial electrophysiological parameters of the 55 rabbit abdomen skin specimens. The electric parameters were analyzed in a modified Ussing chamber. The resistance (R) of the skin specimens treated with diclofenac gel significantly increased, which could be related to the reduction in the water content in intercellular spaces and, consequently, tighter adhesion of the cells. Increased electric potential (PD) was also observed in the skin specimens treated with diclofenac gel. The increase in both R and PD measured under stationary conditions was most likely caused by a transient and reversible increase in sodium ion transport, as the R and PD values decreased after the diclofenac gel was washed away. However, diclofenac gel did not affect the maximum and minimum PDs measured during stimulations. Therefore, it seems that diclofenac gel does not affect the perception of stimuli in the model system used.
... The level of moisture and hydration of the skin is important for effective receptor stimulation, also by pain stimuli, as well as collagen and elastin production, skin regeneration and maintaining a healthy appearance of the skin [1][2][3][4]. A properly hydrated skin is a barrier for microorganisms and external factors, while retaining the ability of physiological exfoliation, and has the capacity of receiving external stimuli [5][6][7][8][9][10]. Dehydrated skin becomes scratchy, mat, flushed, prone to exfoliation, and the occurring micro-damage leads to increased permeability and influx and activation of immunocompetent cells [4,9,[11][12][13]. ...
... Dehydrated skin becomes scratchy, mat, flushed, prone to exfoliation, and the occurring micro-damage leads to increased permeability and influx and activation of immunocompetent cells [4,9,[11][12][13]. Decreased water content causes accumulation of corneocytes on the epidermal surface and disrupts exfoliation [3,5,14]. ...
... The decreased amount of the flexible and water-binding fibers leads to changes in the permeability of the epidermal barrier, and consequently to disruption of the differentiation and regeneration processes [4,9,10,[14][15][16]. Changes in hydration are accompanied by impaired transport of ions, especially sodium [12,13]. Maintaining physiological transport of water and ions is crucial for skin regeneration after treatments involving breaking skin continuity, as well as during the healing of complicated wounds, especially pressure ulcers, frostbites and burns [5,9,12,13]. Moreover, proper hydration and the associated ion transport are important for the effectiveness of reconstructive, esthetic and cosmetic procedures. ...
Article
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The preservation of physiological transport of ions and water content is particularly important for maintaining the skin barrier, touch and pain stimuli, as well as the initiation of skin regeneration processes, especially after treatments associated with breaking skin continuity and wound healing difficulties. The aim of the study was to assess changes in ion transport, measured as values of transepithelial electric resistance and potential difference in stationary conditions and during mechanical-chemical stimulations, depending on the hydration status of isolated rabbit skin specimens. The specimens were divided into five groups: control (n = 22), dehydrated in 10% NaCl (n = 30), rehydrated after dehydration (n = 26), dried at 37°C (n = 26), and rehydrated after drying (n = 25). Dehydrated tissue samples showed altered resistance compared to the control; this change was maintained regardless of rehydration. In the dehydrated samples, changes in the measured electric potential were also noted, which returned to values comparable with the control after rehydration. Dehydrated skin, regardless of the cause of dehydration, responds with changes in the transport of sodium and chloride ions and the altered cellular microenvironment. It could influence the perception of stimuli, particularly pain, and slow down the regeneration processes.
... In the presence of SP, which triggers a shift towards a chronic PS response, the HPA axis response slows down. Under the chronic exposure to PS, there are several pathological changes in the skin, such as a delay in wound healing [77] and an impairment in skin barrier recovery [108,109]. Chronic PS has been shown to result in a disruption of the skin-barrier, as demonstrated by an increase in TEWL in affected mice [108]. Recent findings have suggested that PS decreases epidermal proliferation and differentiation, disrupts the permeability barrier homeostasis, and decreases the skin integrity of the SC [109]. ...
... Under the chronic exposure to PS, there are several pathological changes in the skin, such as a delay in wound healing [77] and an impairment in skin barrier recovery [108,109]. Chronic PS has been shown to result in a disruption of the skin-barrier, as demonstrated by an increase in TEWL in affected mice [108]. Recent findings have suggested that PS decreases epidermal proliferation and differentiation, disrupts the permeability barrier homeostasis, and decreases the skin integrity of the SC [109]. ...
... Aioi et al. demonstrated that overcrowding PS resulted in dry skin and barrier impairment. The dry skin and barrier disruption have been associated with decrease in compounds important to skin barrier function, e.g., ceramide and pyrrolidone carboxylic acid [108]. Moreover, Choi et al. reported that elevated GC concentration could result in permeability barrier changes and delayed barrier recovery after tape stripping, which is linked to decreased epidermal lipid synthesis, as observed during PS [109]. ...
Article
Full-text available
The hypothalamic–pituitary–adrenal (HPA) axis is one of the body’s neuroendocrine networks that responds to psychological stress (PS). In the skin, there exists a peripheral HPA axis similar to the central axis. Glucocorticoids (GCs) are key effector molecules of the HPA axis and are essential for cutaneous homeostasis. Atopic dermatitis (AD) is a condition typically characterized by a chronic relapsing course that often results in PS. HPA dysfunction is present in AD patients by the decreased response of GCs elevation to stress as compared to those unaffected by AD. Nevertheless, in skin, acute PS activates several metabolic responses that are of immediate benefit to the host. During the acute phase of PS, increased endogenous GCs have been shown to provide benefit rather than by aggravating cutaneous inflammatory dermatoses. However, a chronic T helper cell type 2 (Th2) predominant cytokine profile acts as a negative feedback loop to blunt the HPA axis response in AD. In this article, we reviewed the role of CRF, pro-opiomelanocortin (POMC)-derived peptides, GCs of the HPA, and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in AD, with a discussion of the pathogenetic mechanisms of inflammation and skin barrier functions, including antimicrobial defense, and their association with PS.
... Moreover, it has been demonstrated that long-term activation of the HPA axis due to ''chronic'' stress has deleterious effects on various organs, including the skin (Arck et al. 2006;Fukada et al. 2007). Indeed, chronic stress reportedly induces skin-barrier disruption, as evidenced by an increase in transepidermal water loss (TEWL) in both mice (Aioi et al. 2001) and rats (Fukada et al. 2007). ...
... The results showed that in both rats and humans, the chronic stress-induced elevation of TEWL was significantly inhibited by inhalation of rose essential oil. It has been reported that in mice, skin-barrier disruption (as evidenced by an increase in TEWL) occurs after chronic exposure to stress (Aioi et al. 2001). Furthermore, we recently showed that in rats, chronic stress-induced disruption of the skin barrier can be reduced or prevented by the inhalation of green odor (possibly at least in part through an inhibitory effect on the stress-induced activation of the HPA axis) (Fukada et al. 2007). ...
... The major component of the skin barrier is located in the outermost layer of the skin, the stratum corneum, which consists of corneocytes surrounded by lipid regions (Elias 2005). These intercorneocyte lipids play a very important role in skin-barrier function (Rawlings and Harding 2004) and are reportedly reduced in chronically stressed animals (Aioi et al. 2001;Choi et al. 2005). We recently reported that inhalation of green odor prevented the decrease in intercorneocyte lipids seen in chronic stress-exposed rats (Fukada et al. 2007). ...
Article
In stressed animals, several brain regions (e.g., hypothalamic paraventricular nucleus [PVN]) exhibit neuronal activation, which increases plasma adrenocorticotropic hormone (ACTH) and glucocorticoids. We previously reported that so-called "green odor" inhibits stress-induced activation of the hypothalamo-pituitary-adrenocortical axis (HPA axis) and thereby prevents the chronic stress-induced disruption of the skin barrier. Here, we investigated whether rose essential oil, another sedative odorant, inhibits the stress-induced 1) increases in PVN neuronal activity in rats and plasma glucocorticoids (corticosterone [CORT] in rats and cortisol in humans) and 2) skin-barrier disruption in rats and humans. The results showed that in rats subjected to acute restraint stress, rose essential oil inhalation significantly inhibited the increase in plasma CORT and reduced the increases in the number of c-Fos-positive cells in PVN. Inhalation of rose essential oil significantly inhibited the following effects of chronic stress: 1) the elevation of transepidermal water loss (TEWL), an index of the disruption of skin-barrier function, in both rats and humans and 2) the increase in the salivary concentration of cortisol in humans. These results suggest that in rats and humans, chronic stress-induced disruption of the skin barrier can be limited or prevented by rose essential oil inhalation, possibly through its inhibitory effect on the HPA axis.
... Such stress-induced activations of the sympathetic nervous system and hypothalamo-pituitary-adrenocortical (HPA) axis (DiMicco et al. 2006), if they continue for a while, can have deleterious effects on various organs, including the skin (Arck et al. 2006). Indeed, it has been shown in mice that chronic exposure to stress results in a disruption of the skinbarrier function, as evidenced by an increase in transepidermal water loss (TEWL; Aioi et al. 2001). The major component of this barrier is located in the outermost layer of the skin, the stratum corneum, which consists of corneocytes surrounded by lipid regions (Elias 2005). ...
... The major component of this barrier is located in the outermost layer of the skin, the stratum corneum, which consists of corneocytes surrounded by lipid regions (Elias 2005). These intercorneocyte lipids play a very important role in skin-barrier function (Rawlings and Harding 2004) and are reportedly reduced in chronically stressed animals (Aioi et al. 2001; Choi et al. 2005). It has been shown that recovery from the ''acute,'' ''artificially'' produced skin-barrier disruption induced by tape stripping is delayed by such forms of stress as immobilization or exposure to a novel environment, an effect of stress that can be blocked by sedative drugs and some odorants (Denda et al. 1998; Denda, Tsuchiya, Elias, Feingold 2000; Denda, Tsuchiya, Shoji, Tanida 2000). ...
... possibility, the effects of body weight loss per se on skin function should be determined in the near future. In line with a previous report showing wrinkle formation of the skin in stressed mice (Aioi et al. 2001 ), our lightmicroscope examination revealed wrinkle formation in the vehicle + stress group. This effect was not present in the green odor + stress group, which may be another example of a relieving effect of green odor inhalation. ...
Article
We investigated whether inhalation of green odor (a mixture of equal amounts of trans-2-hexenal and cis-3-hexenol) prevents the skin-barrier disruption induced by chronic restraint stress in rats. To this end, transepidermal water loss (TEWL) was measured as an index of the disruption of skin-barrier function, whereas light- and electron-microscope examinations were performed to observe histological changes in the skin of the stressed animals. In addition, the effects on TEWL induced by chronic administration of a glucocorticoid, dexamethasone (DEX), were examined. Chronic restraint stress (8 h per day for 14 days) increased TEWL (vehicle + stress group). This effect (and the chronic stress–induced increase in adrenal weight) was prevented in rats that inhaled green odor at the beginning of each day's restraint (2 h each day for 14 days; green odor + stress group). Electron-microscope studies revealed that rats in the green odor + stress group possessed sufficient intercorneocyte lipids to create an effective skin barrier, although these had apparently been decreased in the vehicle + stress group. Daily administration of DEX for 14 days increased TEWL. The present results suggest that chronic stress–induced disruption of the skin barrier in rats can be reduced or prevented by green odor (possibly at least in part through an inhibitory effect on the stress-induced activation of the hypothalamo-pituitary-adrenocortical axis).
... The quantification of CORT levels is a parameter to determine the magnitude and time course of stress response to different conditions (Bhatnagar & Vining, 2003). In rats exposed to OVCR, VEHI implanted subjects showed a significant CORT increment, relatively fast when compared with previous OVCR studies (Aioi, Okuda, Matsui, Tonogaito & Hamada, 2001), this increment was absent in those subjects implanted with PROG ( Figure 2B) the latter finding is in agreement with other reports which found that PROG proved to have an inhibitory effect on CORT increase (Higashi et al., 2005). Additionally, PROG has shown an inhibitory effect on stress-induced immunosupression (Mediratta et al., 2003) and neurosteroids like dehydroepiandrosterone demonstrate a protective role against immobilization stress and exogenous CORT (Hu, Cardounel, Gursoy, Anderson & Kalimi, 2000). ...
... In support of our findings, there are studies showing an increased exploration in rats by CORT treatment (Osborn, Kim, Steiger & Weinberg, 1998). Alternatively, other studies have reported a diminution on exploratory behavior (Aioi et al., 2001;Kovach, Nearing & Verrier 2001). However they exposed animals to more acute stress with no social characteristics or diffferent models of social stress in distinct species, and with alternative exploration patterns. ...
Article
Full-text available
The hippocampus is sensitive to high levels of glucocorticoids during stress responses; it suffers biochemical and cellular changes that affect spatial memory and exploratory behavior, among others. We analyzed the influence of the neurosteroid progesterone (PROG) on stress-induced changes in urinary corticosterone (CORT) levels, spatial memory and exploratory behavior. Castrated adult male rats were implanted with PROG or vehicle (VEHI), and then exposed for ten days to chronic stress created by overcrowding or ultrasonic noise. PROG and CORT levels were assessed in urine using high-performance liquid chromatography (HPLC). Implanted PROG inhibited the rise of stress-induced CORT, prevented spatial memory impairment in the Morris water maze, and eliminated increased exploratory behavior in the hole-board test. These results suggest a protective role of PROG, possibly mediated by its anxiolytic mechanisms, against corticosteroids elevation and the behavioral deficit generated by stressful situations.
... Stress has been suggested to negatively affect barrier permeability and homeostasis in the skin [4]. Mental stress has been shown to reduce lipogenesis and delay recovery of the skin barrier [1]. We believe that it is necessary to clarify the relationships between stress and skin conditions to reduce the number of patients with skin diseases. ...
Article
In modern society, stress caused by relationships and emotions is one of the greatest social problems. Similar to humans, domestic and captive animals live under various stresses. Several stresses have been associated with skin disorders, such as atopic dermatitis, but there is a lack of reliable and objective indicators for the characterization of this association. This study aimed to define the changes in fatty acid composition and amino acid concentration in the skin following repeated restraint stress in ICR mice. Mice subjected to 30 min of daily restraint stress for 8 days showed changes in the composition of saturated fatty acids, such as an increase in palmitic acid content, which are the substrates of Δ-9 desaturase. Conversely, unsaturated fatty acids decreased with stress treatment, which appeared to be a result of these fatty acids being the substrate of Δ-6 desaturase. Changes in fatty acid composition after stress treatment may be one of the factors that cause skin inflammation. The water-retention capacity may have been lowered by stress treatment because histidine and leucine, which are natural moisturizing factors, were significantly decreased. The collagen content in the skin gradually decreased after repeated stress treatment. Our results indicate that repeated restraint stress may impact skin health through changes in both the fatty acid composition and amino acid concentration in mice.
... Skin is one of the main interfaces between human body and external environment and is one of the main barriers to prevent pathogens to invade human body. The main function of the skin is to act as a physical barrier to protect our bodies from potential attack by foreign organisms, toxins, or any other external physical, chemical, or organic factors (128). The built environment may affect the skin through the following mechanisms. ...
Article
Full-text available
Background: Acne vulgaris is known as a commonly-seen skin disease with a considerable impact on the quality of life. At present, there have been a growing number of epidemiological, medical, demographic and sociological researches focusing on various influencing factors in the occurrence of acne. Nevertheless, the correlation between environmental factors and acne has yet to be fully investigated. Objective: To assess the impacts of individual, natural and social environmental factors on acne and to construct a framework for the potential impact of built environment on acne. Methods: A thorough review was conducted into the published social demographical, epidemiological, and environmental studies on acne through PubMed, Google Scholar and Web of Science, with reference made to the relevant literature. Results: The influencing factors in acne are classed into four major categories. The first one includes individual socioeconomic and biological factors, for example, gender, age, economic level, heredity, obesity, skin type, menstrual cycle (for females), diet, smoking, cosmetics products, electronic products, sleep quality and psychological factors. The second one includes such natural environmental factors as temperature, humidity, sun exposure, air pollution and chloracne. The third one relates to social environment, including social network and social media. The last one includes built environmental factors, for example, population density, food stores, green spaces, as well as other built environment characteristics for transport. Acne can be affected negatively by family history, overweight, obesity, oily or mixed skin, irregular menstrual cycles, sugary food, greasy food, dairy products, smoking, the improper use of cosmetics, the long-term use of electronics, the poor quality of sleep, stress, high temperature, sun exposure, air pollution, mineral oils and halogenated hydrocarbons. Apart from that, there are also potential links between built environment and acne. Yang et al. Acne Conclusions: It is necessary to determine the correlation between the built environment and acne based on the understanding of the impact of traditional factors (sociology of population and environment) on acne gained by multidisciplinary research teams. Moreover, more empirical studies are required to reveal the specific relationship between built environment and acne.
... Overcrowding stress in mice caused higher transepidermal water loss, lower water retention property and impaired barrier function, leading to moderate exfoliation and slight wrinkle formation. The exact mechanism is still unclear, but a decrease in ceramide and pyrrolidone carboxylic acid was observed [151,152]. Other studies have corroborated the result and further confirmed the involvement of stress by demonstrating that treatment of glucocorticoid receptor antagonist or CRH receptor antagonist can block the adverse events [153,154]. ...
Chapter
The intricate relationship between stress and skin conditions has been documented since ancient times. Recent clinical observations also link psychological stress to the onset or aggravation of multiple skin diseases. However, the exact underlying mechanisms have only been studied and partially revealed in the past 20 years or so, involving both the central and peripheral pathways. Psychological stress can play important roles in skin’s inflammation responses, barrier function, and wound healing. Long-term chronic stress can also lead to premature skin aging. In this chapter, the authors will discuss the recent discoveries in the field of “brain-skin connection,” summarizing findings from the overlapping fields of psychology, endocrinology, skin neurobiology, skin inflammation, immunology, and pharmacology.
... Overcrowding stress in mice caused higher transepidermal water loss, lower water retention property and impaired barrier function, leading to moderate exfoliation and slight wrinkle formation. The exact mechanism is still unclear, but a decrease in ceramide and pyrrolidone carboxylic acid was observed [151,152]. Other studies have corroborated the result and further confirmed the involvement of stress by demonstrating that treatment of glucocorticoid receptor antagonist or CRH receptor antagonist can block the adverse events [153,154]. ...
Chapter
The intricate relationship between stress and skin conditions has been documented since ancient times. Recent clinical observations also link psychological stress to the onset or aggravation of multiple skin diseases. However, the exact underlying mechanisms have only been studied and partially revealed in the past 20 years or so, involving both the central and peripheral pathways. Psychological stress can play important roles in skin’s inflammation responses, barrier function, and wound healing. Long-term chronic stress can also lead to premature skin aging. In this chapter, the authors will discuss the recent discoveries in the field of “brain-skin connection,” summarizing findings from the overlapping fields of psychology, endocrinology, skin neurobiology, skin inflammation, immunology, and pharmacology.
... Overcrowding stress in mice caused higher transepidermal water loss, lower water retention property and impaired barrier function, leading to moderate exfoliation and slight wrinkle formation. The exact mechanism is still unclear, but a decrease in ceramide and pyrrolidone carboxylic acid was observed [151,152]. Other studies have corroborated the result and further confirmed the involvement of stress by demonstrating that treatment of glucocorticoid receptor antagonist or CRH receptor antagonist can block the adverse events [153,154]. ...
Article
Full-text available
The intricate relationship between stress and skin conditions has been documented since ancient times. Recent clinical observations also link psychological stress to the onset or aggravation of multiple skin diseases. However, the exact underlying mechanisms have only been studied and partially revealed in the past 20 years or so. In this review, the authors will discuss the recent discoveries in the field of “Brain-Skin Connection”, summarizing findings from the overlapping fields of psychology, endocrinology, skin neurobiology, skin inflammation, immunology, and pharmacology.
... 5-HTR1A levels decreased in both CRS and CUMS mice, a phenomenon that is either because of direct action of cortisol on gene transcription [60] and/or feedback inhibition [61]. Chronic stress may have impacts on the skin barrier, thereby worsening skin diseases [62]. As 5-HTR1A is expressed in the outer part of the epidermis [27], alterations of this receptors in chronic stress may modulate the protective function of this barrier. ...
Article
Full-text available
Stress has been reported to induce alterations of skin pigmentary response. Acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT) whereas chronic stress causes a decrease. 5-HT receptors have been detected in pigment cells, indicating their role in skin pigmentation. To ascertain the precise role of 5-HT in stress-induced pigmentary responses, C57BL/6 mice were subjected to chronic restraint stress and chronic unpredictable mild stress (CRS and CUMS, two models of chronic stress) for 21 days, finally resulting in abnormal pigmentary responses. Subsequently, stressed mice were characterized by the absence of a black pigment in dorsal coat. The down-regulation of tyrosinase (TYR) and tyrosinase-related proteins (TRP1 and TRP2) expression in stressed skin was accompanied by reduced levels of 5-HT and decreased expression of 5-HT receptor (5-HTR) system. In both murine B16F10 melanoma cells and normal human melanocytes (NHMCs), 5-HT had a stimulatory effect on melanin production, dendricity and migration. When treated with 5-HT in cultured hair follicles (HFs), the increased expression of melanogenesis-related genes and the activation of 5-HT1A, 1B and 7 receptors also occurred. The serum obtained from stressed mice showed significantly decreased tyrosinase activity in NHMCs compared to that from nonstressed mice. The decrease in tyrosinase activity was further augmented in the presence of 5-HTR1A, 1B and 7 antagonists, WAY100635, SB216641 and SB269970. In vivo, stressed mice received 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP), a member of the class of selective serotonin reuptake inhibitors (fluoxetine; FX) and 5-HTR1A/1B agonists (8-OH-DPAT/CP94253), finally contributing to the normalization of pigmentary responses. Taken together, these data strongly suggest that the serotoninergic system plays an important role in the regulation of stress-induced depigmentation, which can be mediated by 5-HT1A/1B receptors. 5-HT and 5-HTR1A/1B may constitute novel targets for therapy of skin hypopigmentation disorders, especially those worsened with stress.
... Mice back skin tissue was homogenized with Ultra Turrax (10,000 rpm, 20 s) in cold chloroform (1:3 w/v). Lipid was extracted and quantitated by the previous methods (Aioi, Okuda, Matsui, Tonogaito, & Hamada, 2001). ...
... In the present study, we address one such problem by comparing the SR of two groups of mice (Mus musculus) that were maintained under increasing crowding conditions and fed either control diet (NFD) or high fat diet (HFD). Overcrowding is a most commonly employed method to produce a state of social stress in murine models [20,21]. Supplementation of murine diet with slightly higher amount of dietary fat has been shown to increase the SR in mice [22,23]. ...
Article
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Adaptive theory predicts that mothers would be advantaged by adjusting the sex ratio of their offspring in relation to their offspring's future reproductive success. In the present study, we tested the effect of housing mice under crowded condition on the sex ratio and whether the fat content of the diet has any influence on the outcome of pregnancies. Three-week-old mice were placed on the control diet (NFD) for 3 weeks. Thereafter the mice were allotted randomly to two groups of 7 cages each with 4, 6, 8, 10, 12, 14, and 16 mice in every cage to create increasing crowding gradient and fed either NFD or high fat diet (HFD). After 4 weeks, dams were bred and outcomes of pregnancy were analyzed. The average dam body weight (DBW) at conception, litter size (LS) and SR were significantly higher in HFD fed dams. Further, male biased litters declined with increasing crowding in NFD group but not in HFD. The LS and SR in NFD declined significantly with increasing crowding, whereas only LS was reduced in HFD group. We conclude that female mice housed under overcrowding conditions shift offspring SR in favor of daughters in consistent with the TW hypothesis and high fat diet reduces this influence of overcrowding.
... Furthermore, 5-HT1AR levels decrease acutely in connection with stress, a phenomenon that is either because of the direct action of cortisol on gene transcription (75) and ⁄ or feedback inhibition (55). Chronic stress may have impact on the skin barrier, thereby worsening inflammatory skin diseases such as atopic eczema (76). As 5-HT1AR is expressed in the outer part of the epidermis (58), a change of this receptor in chronic stress or during application of glucocorticoids might modulate the protective function of this barrier. ...
Article
Serotonin (5-hydroxytryptamine; 5-HT) is an important mediator of bidirectional interactions between the neuroendocrine system and the skin. The rate of synthesis of 5-HT from l-tryptophan can be enhanced by brain-derived neuronal growth factor, cytokines, exposure to ultraviolet light and steroids. The major source of 5-HT in the skin are platelets, which, upon aggregation, release this biogenic amine. Moreover, the epidermal and dermal skin express the enzymes required for the transformation of tryptophan to 5-HT, and certain skin cells, such as melanocytes, have been demonstrated to produce 5-HT. In addition, rodent mast cells produce 5-HT, but human mast cells have not yet been fully examined in this respect. Skin cells express functionally active, membrane-bound receptors for 5-HT, as well as proteins that transport 5-HT. The interactions of 5-HT with these various proteins determines the nature, magnitude and duration of serotonergic responses. The immune and vasculature systems in the skin are traditional targets for bioregulation by 5-HT. Moreover, recent findings indicate that keratinocytes, melanocytes and dermal fibroblasts also respond to this amine in various ways. Thus, mammalian skin is both a site for the production of and a target for bioregulation by 5-HT. This indicates that agonists and antagonists directed towards specific 5-HT receptors could be useful in connection with treatment of skin diseases. Based on our increasing knowledge concerning these receptors and their plasticity, future research will focus on the development of serotonergic drugs that exert metabotrophic effects on the cells of the skin without affecting the central nervous system.
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Background: Technology use is at an all-time high and its potential impact on psychological and physiologic health should be explored. Objective: The objective of this narrative review was to identify the role of technology use on health and well-being. Materials and methods: Authors performed a review of PubMed and publications of the World Health Organization, Department of Defense, and Centers for Disease Control and Prevention to determine the impact of technology regarding electromagnetic radiation (EM), posture and mobility, sleep disturbance, and psychological stress and well-being. Results: Studies on the impact of EM were conflicting, with about 45% reporting negative consequences and 55% reporting no effect. Radiofrequency EM (RF-EM) may more significantly affect fibroblasts and immature cells. Device use was implicated in worsening cognitive focus, imbalance, and sleep. Social media use affects self-esteem and mental health and is associated with up to 33% presence of addiction. Effects seem to be dose related and more pronounced in younger ages. Conclusion: Technology use significantly affects sleep, mental health, and cognitive function. Seeking psychological help, limiting social media use, and reducing use before sleep may partially mitigate these effects. The impact of EM is undetermined, but the WHO lists RF-EM as a potential carcinogen.
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Background: Stress may have various effects on our bodies. In particular, the skin may be readily influenced by stress. In addition, there are individual differences in the way we feel stress, suggesting the involvement of genetic factors in such individual differences. Objectives: In this study, we analysed the influence of stress on skin condition and ageing involving Japanese females, and investigated single nucleotide polymorphisms (SNPs) that influence perceived stress of an individual. Methods: We collected genotype data from 1200 Japanese females. At the same time, a questionnaire was conducted on the degree of stress that each subject feels on a daily basis and the current skin condition. We analysed the effects of stress on skin condition and searched for SNPs related to individual stress susceptibility by genome-wide association studies. Results: Our data suggested that stress influences skin condition and ageing, as previously reported. And, we found rs74548608 as a SNP that affects perceived stress of an individual. This SNP is located on the upstream of Patched-1, which is a gene that functions as a sonic hedgehog receptor. Conclusions: Our study has identified new genetic factors for perceived stress of an individual in the Japanese female. The SNP found in this study may be a candidate factor important for understanding the perceived stress of an individual of Japanese.
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Psychological stress is a common factor that can aggravate clinical symptoms of atopic dermatitis. To understand this process, it is necessary to keep in mind that the stress response is a complex and precisely regulated interaction of the central nervous system, peripheral nervous system, skin, and immune system. By reviewing this complex network, clinicians can explain how psychological stress can affect stress response and identify possible treatment strategies that can be utilized for patients to relieve stress-induced aggravation of atopic dermatitis.
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This article is a review of current evidence to both support and refute holistic approaches to dermatological cases, including analysis of data linked to psychodermatology, psychosocial and lifestyle influences. A case for taking an integrated approach adjuvant to traditional medicine in skin disease therapy, how this could save time, money and reduce pressure on resources will be discussed. Overall, the research is promising; however, there are gaps in knowledge and there is a need for long-term, larger scale studies in the future. Also, an improved understanding of the processes that lead to inflammatory cutaneous diseases in the future will enable practitioners to make better treatment choices.
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Introduction The epidermal barrier functions to limit skin infection and inflammation by inhibiting irritant and immunogen invasion. Abundant evidence suggests that psychological stress stemming from crowding, isolation, nicotine smoking, insomnia, mental arithmetic tasks, physical pain, real life‐stressors (examinations and marital strain), and lack of positive personality traits may impart both acute and chronic epidermal dysfunction. Materials/Methods A review of PubMed and EMBASE databases was conducted to identify all English case‐control, cross‐sectional, and randomized control trials that report the effect of stress on epidermal barrier function. The authors’ conclusions are based on available evidence from 21 studies that met the inclusion and exclusion criteria. Results Psychological stressors upregulate the hypothalamic‐pituitary‐adrenal axis to stimulate local and systemic stress hormone production, ultimately leading to aberrant barrier dysfunction, characterized by decreased epidermal lipids and structural protein production, decreased stratum corneum hydration, and increased transepidermal water loss. Discussion This evidence‐based review explores the adverse effects of psychological stressors on epidermal barrier function. Future investigations using more real‐life stressors are needed to further elucidate their impact on skin physiology as well as to identify practical stress‐relieving therapies that minimize and restore epidermal barrier dysfunction, particularly in at‐risk populations. This article is protected by copyright. All rights reserved.
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Accurately evaluating the factors that exacerbate atopic dermatitis is helpful in management of this skin condition. Psychological stress is a major exacerbating factor and often aggravates atopic dermatitis. The most common symptoms of atopic dermatitis themselves can also act as secondary stressors and lead to a deterioration in quality of life. Moreover, patients with atopic dermatitis may also suffer from other mental disorders such as depression and anxiety. It is known that psychological stress is associated with abnormal skin barrier function and a shift toward cytokine expression in T-helper 2 cells. The stress response affects three systems: the hypothalamic-pituitary-adrenal axis, which regulates the release of adenocorticotropin and cortisol; the sympathoadrenal medullary axis, which regulates the release of catecholamines; and the neurotrophin neuropeptide axis, which regulates the release of substance P. Therefore, treatment for psychological stress is quite important for controlling skin barrier function and inhibiting immune activation in cases of atopic dermatitis. Treatments for psychological stress include pharmacotherapy, such as topical corticosteroids, and psychotherapy, such as relaxation exercises, coping skills training, and stress management instruction.
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Normale Haut ist definiert als Zustand ohne sichtbare Läsionen und ohne Empfindungen des Unwohlseins [4]. Dieser Zustand resultiert aus einem Gleichgewicht diverser physiologischer Parameter einschließlich Feuchtigkeitsgehalt, Talgproduktion, Verhornung und Abschuppung. Trockene Haut (Xerosis cutis) ist ein Hautzustand, der angeboren und erworben sein kann. Dieser Hautzustand, der, wie Ergebnisse einer eigenen Untersuchung bestätigen, sehr häufig ist, kann so geringfügig ausgeprägt sein, dass er nur eine kosmetische Beeinträchtigung darstellt, kann aber bei maximaler Ausprägung auch zu einer schweren Dermatose führen. Jedoch kommt in der Dermatokosmetik gerade der milden Xerosis cutis eine wichtige Bedeutung zu, auch was die Beratung hinsichtlich einer hautzustandsgerechten Hautreinigung und Hautpflege anbelangt.
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In many species, chronic stress due to overcrowding during the juvenile period triggers several metabolic and behavioral pathologies in adulthood. The aim of this study was to determine whether a chronic stress condition (overcrowding) induces changes in plasma and hair corticosterone concentrations, overall growth, and organ weights in young Wistar rats. The experimental subjects were divided into 2 groups (control and overcrowded); the overcrowded subjects were exposed to overcrowding during days 38 through 65 after birth. Plasma and hair corticosterone concentrations were higher in overcrowded rats compared with control subjects. In addition, overcrowding reduced body and organ weight gains. These results demonstrate that measuring the concentration of corticosterone in hair samples is an effective, noninvasive method for monitoring chronic stress in rats. © 2016 by the American Association for Laboratory Animal Science.
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Normale Haut ist definiert als Zustand ohne sichtbare Läsionen und ohne Empfindungen des Unwohlseins [4]. Dieser Zustand resultiert aus einem Gleichgewicht diverser physiologischer Parameter einschließlich Feuchtigkeitsgehalt, Talgproduktion, Verhornung und Abschuppung. Trockene Haut (Xerosis cutis) ist durch einen Feuchtigkeitsmangel in der Hornschicht der Haut charakterisiert. Somit betrifft der Zustand einer trockenen Haut anatomisch lediglich die obersten, nicht mehr stoffwechselaktiven Anteile der Epidermis, das Stratum corneum. Ein normales Stratum corneum speichert etwa 10 bis 20% Wasser, bei niedrigerem Wassergehalt kommt es zur subjektiven Empfindung einer trockenen Haut [14]. Es existieren prinzipiell zwei Faktoren, die an der Entwicklung der Xerosis cutis beteiligt sind: 1. Dehydratation der Hornschicht durch eine gestörte epidermale Barrierefunktion mit erhöhtem transepidermalen Wasserverlust (TEWL) und 2. Störungen der Verhornung von Keratinozyten. Die epidermale Barriere kann z. B. durch eine unphysiologische Quantität und/oder Zusammensetzung der Hautlipide (z. B. bestimmter Ceramide) in ihrer Integrität gestört sein.
Article
Stratum corneum intercellular lipids regulate skin water barrier function and water-holding capacity; their modification may impair these properties. Physical and chemical stresses diminish barrier function. Acute barrier disruption by tape stripping increases sphingomyelinase and serine palmitoyltransferase activity; ceramide contents are increased to restore barrier function. Overcrowding stress induces dry skin, and the barrier function impairment correlates with decreased skin cera- mides. The effect of UV irradiation on ceramide content and barrier function varies with doses and UV wavelength. Stress-induced ceramide generation may induce apoptosis in cultured human keratinocytes and restore barrier function. This review focuses on the role of ceramides in physical and chemical stress, suggesting that refinement and extension of this academic domain may lead to therapeutic advances.
Article
Inflammatory skin disorder aggravates when a horrific memory is evoked, but the mechanism of this effect is unclear. The objective of the present study was to examine the effects of evocation of a horrific memory on the skin and mast cells in an animal model. A sound stimulus linked to an electric shock was given to C57BL/6 mice (7-week old, males). One, 3 and 5 days later, the mice received the sound stimulus again. The reactions of mice that received the initial sound stimulus were compared with those of mice that did not receive the initial stimulus. A freezing phenomenon was observed when the sound stimulus was given to mice that received the initial stimulus, which indicated evocation of a past memory of fear. The degranulation rate of dermal mast cells and the length of substance P (SP)-positive nerve fibers of the skin significantly increased on days 1 and 3, the SP level decreased significantly, and the number of SP-expressing cells in the dorsal root ganglion significantly increased on day 1. These findings suggest that prior experience of severe stress linked to a stimulus subsequently evokes fear associated with the same stimulus and results in activation of dermal mast cells and skin nerves.
Article
Collagen (JC) was extracted from jellyfish (Rhopilema esculentum) and hydrolyzed to prepare collagen hydrolysate (JCH). The protective effects of JC and JCH against UV-induced damages to mice skin were evaluated and compared in this article. JC and JCH could alleviate the UV-induced abnormal changes of antioxidative indicators, including the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities and the contents of glutathione (GSH) and malondiaidehyde (MDA). JC and JCH could protect skin lipid and collagen from the UV radiation damages. Furthermore, the changes of total ceramide and glycosaminoglycan in skin were recovered significantly by JC and JCH. The action mechanisms mainly involved the antioxidative properties and the repairing to endogenous collagen synthesis of JC and JCH in vivo. JCH with the lower molecular weight showed much higher effects than JC. The results indicated that JCH was a novel antiphotoaging agent from natural resources.
Article
1. Eczema impairs the quality of life of both sufferers and carers. 2. Emollients play a major part in the skin care of eczema. 3. Care needs to be taken to ensure correct strength and dose of topical steroids when used. 4. All practitioners need to be aware of the range conventional and complementary therapies on offer to eczema sufferers.
Article
The effects of five levels of population density on various organs, the neuroendocrine system, skin function, skin blood perfusion, and blood parameters were studied in the hairless mouse. Skin barrier recovery was evaluated by measuring transepidermal water loss after tape stripping. Blood perfusion was measured by means of a laser Doppler imaging technique. The effect of a parasympathetic nerve stimulator, carpronium chloride, on skin function in the crowded animal model was also examined. A 7 d crowding (10, 15, 20 mice/cage) significantly increased the levels of corticosterone, catecholamines (norepinephrine, epinephrine and dopamine), glucose and serum lactate dehydrogenase activity in circulating blood, induced atrophy of kidney, ovary and thymus and hypertrophy of adrenal glands, and decreased body weight gain in comparison with the control (5 mice/cage). Crowding also increased epidermal thickness and epidermal proliferative activity, and decreased corneocyte size, rate of barrier recovery and skin blood perfusion. Most of these changes became more marked with increasing population density and/or longer exposure to a crowded environment. Isolation (1 mouse/cage) increased the level of norepinephrine and rate of skin blood perfusion, and significantly delayed barrier recovery. Repeated topical applications of carpronium chloride for 7 d improved the changes in skin blood perfusion, barrier recovery, kidney and ovary, and epidermal morphology induced by crowding. The crowded animal model could be useful for quantifying objectively the influence of crowded environment-induced stress on cutaneous function and blood perfusion.
Article
Stress significantly influences skin diseases and cutaneous functions. Recently, interactions between stress and skin conditions have been studied in animal models using various systemic stressors. Here, we studied the effect of intermittent foot shock stress on the hair cycle of C57BL/6 mice. After a 2-week period of intermittent foot shock stress, we examined the changes in the depilation-synchronized hair cycle macroscopically and histologically and we also measured the plasma levels of corticosterone. We found that foot shock stress prolonged the telogen stage and delayed the subsequent anagen induction in the hair cycle. The distribution patterns of corticotrophin releasing factor or corticotrophin releasing factor receptor positive cells in the skin of stressed or of control mice were identical with those in the ordinal hair cycle. It is noteworthy that corticotrophin releasing factor positive keratinocytes were observed in the telogen follicles of the stressed mice but were negative in the telogen follicles of the non-stressed mice in this study. Plasma corticosterone levels were significantly higher in the stressed group than in the control group. These results suggest that increased levels of plasma corticosterone may be involved in the mechanism underlying the stress-induced delay of the hair cycle.
Article
This work analyses the main studies dealing with the mechanisms by which the brain is altered by chronic stress and the impact of social stimuli on the activation of these mechanisms, which can lead to behavioural disorders and cognitive impairment in communities of mammals. The physiological and hormonal responses triggered as a response to stress are linked to alterations in certain areas of the brain and more particularly in the hippocampus. These mechanisms include hyperactivity of the hypothalamus-pituitary-adrenal axis, raised levels of corticosteroids and excitatory amino acids, neurotoxicity due to intracellular accumulation of calcium, apoptosis and a number of factors having to do with the immunological system. Most of these studies have involved the exogenous application of supraphysiological levels of corticosteroids or challenging the individual with stimuli that do not properly belong to their natural surroundings. Nevertheless, it is also possible that these mechanisms are triggered by aversive social stimuli from the natural environment, such as confrontation, establishing hierarchies, neglect and social evaluation. It has been proved that social stress has important effects on conduct and health, especially with regard to the structural and functional integrity of the brain. Social stress can trigger important alterations in the nervous system of individuals exposed to it and these changes can manifest themselves as varying types of disorders affecting conduct and the cognitive skills. Nevertheless, not all natural surroundings give rise to these adverse effects, as balanced communities offer their members support, protection and a series of other advantages.
Article
The effects of housing on the onset time and prevalence of wet skin lesions were investigated in NOA mice, which spontaneously develop these lesions at a high rate. Wet skin lesions developed earliest in mice that were housed individually. For mice that were housed in groups, the lesions developed earlier in mice with non-littermate group housing than in mice with littermate group housing. The prevalence of lesions was in the following order: individual housing > non-littermate group housing > littermate group housing. These results suggest that socio-psychological factors are involved in the etiology of wet skin lesions in the NOA mouse. Under individual housing conditions, two other novel characters of the NOA mouse were also observed, specifically, development of dry skin and wet skin lesions at the tail root. These characteristics developed early and with high prevalence and were easily observed on external examination. Therefore, these novel characteristics observed in NOA mice are potential markers of the psychological state of the animals.
Article
In a previous study, we reported the development of grossly observable dry skin in all of the Naruto Research Institute Otsuka Atrichia (NOA) mice that were housed individually. In the present study, dermal physiological function tests were conducted and the usefulness of this dry skin model for evaluating the efficacy of topical moisturizers was assessed. As a result, we have confirmed a marked reduction in the water content of the stratum corneum in these animals. Therefore, the development of dry skin in the NOA mouse strain under individual housing conditions may be expected to serve as a useful animal model for evaluating topical moisturizers. Specifically, the water content of the stratum corneum was restored in proportion to the oil content of the ointment base used to treat the animals, and the moisturizing effects of urea were confirmed in animals treated with urea-containing ointment. In addition, when the animals that had been housed individually were returned to group housing conditions, the water content of the stratum corneum was restored, with a corresponding improvement in dry skin. This finding suggests that socio-psychological factors are involved in the etiology of dry skin in individually housed NOA mice.
Article
The interaction between nerves and mast cells can effect regulation of the immune system and inflammatory responses. Recent studies have shown that various stressors can induce degranulation of dermal mast cells in animals. This study was conducted to confirm that substance P (SP) was involved in the degranulation of dermal mast cells in stress conditions. Using a communication box system, foot shock stress (FS) and psychological stress (PS) were administered to mice and the degranulation rate of dermal mast cells, the number of SP-positive nerve fibers and changes in SP content were determined. The inhibitory effect of a non-peptide NK1-receptor antagonist on these changes was investigated. Both FS and PS significantly enhanced the degranulation of dermal mast cells and increased the number of SP-positive nerve fibers. FS significantly decreased dermal SP content whereas SP was increased by PS. These changes were inhibited by intraperitoneal injection of NK(1) receptor antagonist. It was considered that SP released from the nerve ending, had an important role in the degranulation of dermal mast cells. Results of this study suggest that the tachykinin receptor antagonist exhibited an inhibitory effect on aggravated stress-induced dermatitis.
Article
Sphingolipids are known to play an important role in both water retention and epidermal permeability barrier function in mammalian stratum corneum. However, little is known about the effects on epidermal function of orally administered sphingolipids. We examined the effect of dietary glucosylceramide (GluCer) on the maintenance and recovery of epidermal barrier function. Hairless mice were fed a particular diet (HR-AD) for 4 weeks to induce chronic skin perturbation. Subsequently, a normal diet supplemented with GluCer (from rice bran and germ) was provided for the next 4 weeks. Transepidermal water loss (TEWL) and stratum corneum flexibility were measured throughout this recovery phase. Additional hairless mice were fed a diet with or without a maize-extracted GluCer supplement for 5 weeks, then their skin was acutely perturbed with repeated tape-stripping, and the TEWL was measured. Although skin functions were generally lower following chronic perturbation, in GluCer-fed mice the TEWL was significantly reduced at 2 weeks and the stratum corneum flexibility was increased at 3 weeks compared to controls. Following acute barrier perturbation by tape-stripping, mice an HR-AD fed a GluCer diet exhibited enhanced recovery compared with the control diet group. These results demonstrate that in hairless mice skin barrier functions impaired by chronic or acute perturbations were improved by dietary GluCer. The oral administration of GluCer may be useful for the preservation and recovery of epidermal barrier functions an HR-AD.
Article
There is an increasing evidence to indicate that stress can influence skin disease and cutaneous functions. Previous studies have shown that stress alters the murine hair cycle; however, these studies have been carried out by using mouse models in which the hair cycle is forcibly synchronized after depilation. To examine whether foot shock stress (FS) changes the spontaneous hair cycle in a non-depilated animal model, and to evaluate the role of mast cells and substance P (SP) in the influence of stress on the hair cycle. Changes in the spontaneous hair cycle and the inhibitory effects of a specific SP NK1 receptor antagonist were examined in non-depilated mice during 3-4 weeks of FS. Foot shock stress prolonged the telogen stage of the hair cycle and delayed the induction of the subsequent anagen stage in the animal model. FS caused an increase in the ratio of de-granulated mast cells in the skin, an increase in the number of TUNEL-positive cells, and a decrease in the number of Ki67-positive cells. The NK1 receptor antagonist, WIN 62577, inhibited these stress responses. Our results strongly support previous work, demonstrating that stress alters active hair-cycling in vivo through the action of SP.
Article
The Guide for the Care and Use of Laboratory Animals (Guide) recommends minimum floor space per mouse based on weight, with no other factors considered. We conducted a randomized experiment to evaluate the effect of housing density on reproductive indices and corticosterone levels in lactating mice. Female mice matched for age, strain, and date-of-pregnancy were housed individually. At parturition the dams were randomly allocated to have litters culled or remain intact. The experimental group had litters culled to meet the Guide's space density requirement. Litters of the second group were maintained as the numbers born to each dam. Fecal corticosterone levels (first-generation mice only), growth, and weaning weights were measured for mice in all cages; in addition, the reproductive behavior of progeny generated under both housing conditions was assessed to determine whether a space x litter size interaction affected subsequent reproduction. The growth rates for pups from culled litters were significantly greater than those from intact litters. The first-generation pups showed no statistically significant differences in fecal corticosterone or reproductive parameters. The second-generation pups showed no statistically significant differences in growth rates. The results of the study suggest that a strict interpretation of space requirements as listed in Table 2.1 of the Guide is not warranted for lactating dams with litters.
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Mice were stressed by overcrowding (20 mice/cage instead of 5-6) for up to 4 weeks. They served either as donors of bone marrow cells for the exogenous spleen colony assay, or as irradiated recipients for the exogenous or endogenous colony assay. The colony counts were in either case suppressed by overcrowding that lasted up to 2 weeks or so before the assay, and were slightly stimulated by prolonged exposure. Neuroendocrine mechanisms affecting the microenvironment, the proliferation rate, and/or the recirculation of hemopoietic cells, were discussed as an alternative to more conventional explanations (e.g., reduced nutrition, increased bacterial load).
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Intracellular calcium concentration is a sensitive marker of the homeostasis of living cells, and its increase is an essential step of T lymphocyte activation. Changes in the environment provoke an adaptive stress-response of the organism. In our present work we have investigated the effect of chronic overcrowding on resting and lectin-stimulated cytoplasmic free calcium concentration of splenic T lymphocytes from young and aged CBA/CA mice (50 animals total). The animals were kept under 'normal' (68 cm2/animal) or 'overcrowded' (22 cm2/animal) conditions for 3 months. Young animals showed no change in resting and stimulated calcium after overcrowding. T cells from aged mice, however, displayed significantly smaller levels of both resting and lectin-stimulated intracellular calcium concentration (p < 0.01 each), as compared to those of the non-stressed, aged animals. This inadequate adaptation in the calcium metabolism of T lymphocytes may significantly contribute to the diminished immune response of the aged in stress.
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Human beings need to adapt to any extreme, unknown, or isolated environment. This adaptation requires changes in the normal regulation of psychophysiological homeostasis, as described in terms of stress reaction. The aim of the present study was to monitor the processes of human adaptation to cold and isolated areas in Antarctica during the 12th expedition of the Italian National Research Program. Nine healthy subjects (experimental subjects), members of the expedition, and nine controls in Italy, were studied over a period of 2 months. Anterior pituitary hormone secretion, insulin, and melatonin, plus routine blood test, blood pressure, and ECG were performed. In addition, psychophysiological correlates were also recorded before and after the expedition period. In experimental subjects results of metabolic data suggested the presence of an increased peripheral insulin sensitivity at the end of the permanence in the station and a significant increased of total cholesterol. Hematocrit also significantly increased due to the conditions of hypobaric hypoxia. Results of endocrine data showed a significant decrease (p < 0.05) of hormone levels, which was associated with a significant decrement of the Galvanic Skin Response (GSR) activity to a standardized cognitive stress. No significant differences were reported in the controls. The data suggest that the exposure to the extreme environment develops a possible psychophysiological mechanism(s) that decreases the individual arousal.
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132 psoriasis patients who had been completely cleared with dithranol were assessed and then followed up over a 3-year period. The incubation time from specific incidents of stress to the development of psoriasis was between 2 days and 1 month. Specific stress within a month before the first attack was recalled by 51 patients (39%); chance association was excluded by studying a control group where there was significantly less specific stress. The prognosis for the psoriasis patients who recollected specific stress a month prior to the onset was significantly better than for the rest of the patients where none had been recalled.
Article
Alleviators of skin irritation were sought and their practical usefulness was evaluated in rats during the development of reaction to lauroylsarcosine (LS), an enhancer of transdermal absorption. LS (0.04–5%) produced erythema in a dose-related manner. Microscopic findings suggested that the damage by LS on keratinocytes caused this skin irritation. In a cultured fibroblast model, vitamin E and squalene were screened as reducers of LS-induced cell damage. Both compounds apparently alleviated 1% LS-induced erythema. Moreover, the combined addition of vitamin E or squalene and LS to isosorbide dinitrate (ISDN) ointment maintained greater penetration and less irritation.
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Proclivity to acute irritant contact dermatitis has been reviewed by comparing the response in patients with atopic dermatitis to controls. Although several controlled studies demonstrate such a proclivity, others do not, suggesting that the mechanisms involved are complex.
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A retrospective assessment of insight was undertaken in 61 patients whose psoriasis was considered to have been precipitated by stress. A significantly better prognosis was observed in those patients assessed as having had insight.
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Stratum corneum sphingolipids are of particular importance in maintaining the water permeability barrier of mammalian epidermis. Free amino acids also play an important role in water retention in the stratum corneum. To clarify the way in which these substances affect scaly skin, stratum corneum sphingolipids and free amino acids collected from artificially-induced scaly skin were analysed. Scaly skin was induced by tape stripping. The total amount of sphingolipids was quantified by gas chromatography and five of sphingolipid fractions were isolated and quantified by thin-layer chromatography. Free amino acids were analysed using a high-speed amino analyser. The total amount of sphingolipid in scaly skin did not differ statistically from that in control skin. However, a significant change in the distribution of the five sphingolipid species was observed in scaly skin and the total amount of amino acids was decreased in scaly skin. These results suggest that the distribution of these five types of sphingolipid and the total amount of amino acids are responsible for scaly skin.
Article
The local sweating response to thermal stress (mean ambient temperature 33 degrees C) was assessed under resting conditions on the non-eczematous back skin of 26 young men with atopic dermatitis (AD) and in 22 non-atopic controls with other dermatoses. The baseline (transepidermal) water loss was separately determined at room temperature (mean 23.6 degrees C) to calculate the pure sweat loss. A gravimetric collecting method was used for the measurements at 40, 60 and 80 min. In the heated room the sweat loss in AD patients was significantly lower at all time intervals. The cumulative sweat loss was 50-60% lower in AD patients than in the controls (P less than 0.02). Subjects with dry AD skin had a lower sweat loss than subjects with normal-looking skin. Compared with controls the sweat loss in AD patients was lowest at 40 min, suggesting a retarded sweating response. Half of the patients with AD and half of the controls had active participation in sports, and showed a greater sweat loss compared to the non-sporting subjects in the same group.
Article
The transferred percentages of 13 drugs to rat skin from transdermal patches were studied to reveal the relationship to their physicochemical properties. The drugs to be tested had melting points of 13.5-234 degrees C, lipophilic indices of 0.475-5.336, and molecular weights of 122.12-392.45. The transferred percentage of drug to intact skin was lower, the higher the melting point, lipophilic index and molecular weight. The same was true in stripped skin, where the transferred percentage of drug was markedly increased. The difference between transferred drug percentages to stripped and intact skin, which could be regarded as the regulatory contribution of the stratum corneum, tended to be larger, the lower the drug's melting point and lipophilic index.
Article
Stratum corneum lipids are an important determinant for both water-retention function and permeability-barrier function in the stratum corneum. However, their major constituent, ceramides, have not been analyzed in detail in skin diseases such as atopic dermatitis that show defective water-retention and permeability-barrier function. In an attempt to assess the quantity of ceramides per unit mass of the stratum corneum in atopic dermatitis, stratum corneum sheet was removed from the forearm skin by stripping with cyanoacrylate resin and placed in hexane/ethanol extraction to yield stratum corneum lipids. The stratum corneum was dispersed by solubilization of cyanoacrylate resin with dimethylformamide, and after membrane filtration, the weight of the stratum corneum mass was measured. The ceramides were quantified by thin-layer chromatography and evaluated as microgram/mg stratum corneum. In the forearm skin of healthy individuals (n = 65), the total ceramide content significantly declined with increasing age. In atopic dermatitis (n = 32-35), there was a marked reduction in the amount of ceramides in the lesional forearm skin compared with those of healthy individuals of the same age. Interestingly, the non-lesional skin also exhibited a similar and significant decrease of ceramides. Among six ceramide fractions, ceramide 1 was most significantly reduced in both lesional and non-lesional skin. These findings suggest that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry skin.
Article
Immobilization stress induced interleukin-1 beta (IL-1 beta) mRNA in the rat hypothalamus. IL-1 beta mRNA was induced at 30 min after the start of immobilization, reached a maximum at 60 min and then was still detected with a decreased level at 120 min. However, 240 min after the start of the immobilization, IL-1 beta mRNA became hardly detectable despite the continuance of immobilization. Distinct expression of IL-1 beta mRNA was not detected in any other brain region examined at 30 and 60 min after the start of immobilization. These results demonstrate that the immobilization stress induces the expression of IL-1 beta mRNA solely in the hypothalamus and suggest that IL-1 beta is involved in the response to stress there.
Article
In order to clarify the possible role of lipids in the water-holding property of stratum corneum, the forearm skin of 6 healthy male volunteers was treated with acetone/ether (1/1) for 1, 5, 10, and 20 min. A prolonged treatment period of 5-20 min produced a chapped and scaly appearance of the stratum corneum without any inflammatory reactions. Under these conditions, there was a marked decrease in the water-holding capacity of the stratum corneum accompanied by a considerable and selective loss of intercellular lipids such as cholesterol, cholesterol esters, and phospholipids. These impairments persisted until day 4 after treatment. Electron microscopic observation of the altered stratum corneum revealed that naturally occurring intercellular materials were absent, leaving the area with the appearance of a vacant space. These findings suggest an additional and essential role of the specific structural lipids for the water-holding properties of the stratum corneum.
Article
Rats were subjected to stress by increasing the number in a cage from 6 to 40 for 6-hr periods for either 2, 4, or 8 days. This treatment produced a rise in serum corticosteroid level which reached a maximum on the fourth day of treatment. The plasma elimination rate of antipyrine was not significantly altered in the stressed animals although the rate of absorption of the drug was decreased. Microsomes prepared from the livers of stressed and control animals indicated that the treatment had differing effects on some of the enzymes responsible for the metabolism of the carcinogen benzo[a]pyrene. Thus, uridine diphosphoglucuronic acid (UDPGA) transferase activity was significantly decreased, aryl hydrocarbon hydroxylase (AHH) and epoxide hydratase (EH) activities were increased, but cytochrome P-450 and glutathione transferase levels in the hepatic microsomes from the treated animals did not differ significantly from those of the controls. The microsome-catalyzed binding of benzo[a]pyrene to DNA was significantly reduced by this stress treatment.
Article
The enhancing capacity of various chemicals, which are widely recognized as enhancers, for the transdermal penetration into full-thickness rat skin of a model lipophilic drug [indomethacin (IND)] and a hydrophilic permeant (urea) was estimated by an in vitro technique. In addition, the fluidity of the stratum corneum lipids, the partitioning of IND into skin, the lipid (ceramides) extraction from the stratum corneum by enhancers, and the IND solubility in enhancer vehicle were measured and related to the enhancing capacity. In vitro permeation experiments with hairless rat skin unequivocally revealed that the enhancers varied in abilities to enhance the fluxes of both agents. Laurocapram, isopropylmyristate (IPM), sodium oleate, and cineol increased fluxes of both agents to a great extent, but N-methyl-2-pyrrolidone (NMP), N,N-diethyl-m-tolamide (DEET), and oleyl oleate were less effective acclerants. Many enhancers increased the fluidity of the lipids [with a threshold of approximately 0.6-0.8 ns at 37 degrees C in the rotational correlation time (tau c)], the skin partitioning of IND, the extraction of ceramides from the cornified cells, and the thermodynamic activity of IND in vehicle (calculated from the solubility) to varying extents. A good correlation was observed between the increase in the fluidity of stratum corneum lipids and the partitioning of IND into skin, between the increase in the fluidity and the flux or the decrease in lag time for IND, between the removal of ceramides and the skin partitioning of IND, and between the removal of ceramides and the flux of urea (p < 0.05 in all cases).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The effects of immobilization-induced stress on plasma testosterone levels and lipogenesis in the sebaceous gland were examined in male Syrian hamsters. To induce immobilization stress, the animals were placed in the prone position and wrapped with flexible steel wire gauze at room temperature. Plasma testosterone levels were determined by radioimmunoassay (RIA) of blood samples and sebaceous lipogenesis was determined by measurement of the incorporation of a lipid precursor, 14C-acetate, in ear skin biopsy samples. Both specimens were obtained immediately after the hamsters were decapitated. Immobilization stress for 4 consecutive days produced a marked fall in plasma testosterone levels and sebaceous lipogenesis. These reductions were reversible, the decreased plasma testosterone levels and decreased sebaceous lipogenesis recovering to the nonstressed or prestimulus levels after approximately 1 week. In 4-day stressed animals in occurrence with a decrease in plasma testosterone, sebaceous lipogenesis in ear with topical application of a small dose of testosterone, which have no effect on plasma testosterone level, was equivalent to that in nonstressed animals. These findings indicated that immobilization-induced stress lowered testosterone secretion, and consequently the testosterone levels in the skin, resulting in decreased lipogenesis in the skin. These results thus suggest that psychological or physiological stress can influence cutaneous function by inducing changes in the neuroendocrine system.
The superficial portion of the stratum corneum (SC), which is always under the influence of various exogenous factors, easily develops firm and brittle skin surface changes, whenever its hydration state is reduced or whenever there is any functionally deficient area of pathological SC that is unable to retain enough water even in the usual ambient conditions. In contrast, the deeper portion of the SC, which is always well hydrated because of its structural closeness to fully water-saturated viable epidermis, does not pose any serious problems as long as the skin is normal. Based on in vivo and in vitro measurements we have established that high-frequency conductance is a non-invasive technique which measures the hydration state of the superficial portion of the SC, the crucial part determining the physical properties of the skin surface.
Article
Previously, we demonstrated that there is a marked reduction in the amount of ceramide in the stratum corneum of both lesional and nonlesional forearms in atopic dermatitis (AD), suggesting that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry and barrier-disrupted skin. In this study, we investigated, as a possible mechanism involved in the ceramide deficiency, whether sphingomyelin (SM) metabolism is altered in AD as compared to normal controls. In stripped stratum corneum and biopsied whole epidermis of patients with AD, SM hydrolysis as measured at pH 4.7 using [choline-methyl-14C]sphingomyelin as a substrate were markedly increased by 27- and 7-fold, respectively. Radio-thin-layer chromatography of the reaction products revealed that, whereas the SM hydrolysis in age-matched normal controls were associated with sphingomyelinase (SMase) that degrades SM to yield ceramides and phosphorylcholine (PC), most of the SM hydrolysis detected in AD were attributable not to the SMase but to a hitherto undiscovered epidermal enzyme, SM acylase, which releases free fatty acid and sphingosyl-PC (Sph-PC) instead of ceramides. The potential of this acylase-like enzyme to generate Sph-PC through SM hydrolysis was corroborated by thin-layer chromatographic analysis of the reaction products obtained using porcine kidney acylase, followed by high-performance liquid chromatography-mass spectrometry. Furthermore, Sph-PC was also detected by high-performance liquid chromatography-mass spectrometry after incubation of SM with atopic stratum corneum samples. On the other hand, the stratum corneum of patients with contact dermatitis or chronic eczema exhibited neither increased SM hydrolysis nor the generation of Sph-PC upon radio-thin-layer chromatographic analysis. These findings suggest that SM metabolism is altered in AD, resulting in a decrease in levels of ceramides, which could be an etiologic factor in the continuous generation of atopic dry and barrier disrupted skin observed in AD.
Article
The studies described here demonstrate that the activation of the physiologic stress response systems of the body can enhance immune function in vivo. This enhancement is observed as a large and long lasting increase in allergic contact sensitivity or delayed-type hypersensitivity, an immune reaction which involves an Ag-specific, cell-mediated immune response. In contrast, acute stress has no effect on the course of irritant contact sensitivity, an immune reaction that does not involve an Ag-specific memory response. A comparison of infiltrating leukocyte numbers in sections of inflamed skin from unstressed and stressed animals shows that stress induces a significant and persistent increase in numbers of leukocytes at the site of the delayed-type hypersensitivity reaction. These results demonstrate that a relatively mild behavioral manipulation can enhance an important class of immune responses that mediate harmful (allergic dermatitis) as well as beneficial (resistance to certain viruses, bacteria, and tumors) aspects of immune function. The implications that these studies have for clinical, diagnostic, and experimental manipulations involving cell-mediated immune function are discussed.
Article
Atopic eczema is a chronic inflammatory skin disease which shares some psychological and neuroendocrine disturbances with patients suffering from depression. In view of recent findings of an attenuated response of the hypothalamic-pituitary-adrenal (HPA) system in patients with atopic eczema during a human corticotropin-releasing hormone (hCRH) challenge paradigm fourteen consecutive non-specifically trained in-patients with atopic eczema (8 men, 6 women) and an age-matched control group (8 men, 6 women) performed exhausting incremental graded bicycle exercise to evaluate cortisol, adrenocorticotropin (ACTH), beta-endorphin, epinephrine and norepinephrine releases induced by physical stress. The exercise yielded significant increases in cortisol, ACTH, beta-endorphin, epinephrine and norepinephrine concentrations in both groups. Patients with severe eczema displayed a significantly lower increase in norepinephrine levels when compared with the less affected patient group. In contrast to the challenge with exogenous hCRH no substantial difference in the net responses of ACTH and cortisol could be detected between patients with atopic eczema and controls using the physical stress paradigm. These substantial differences in the net outcome between both challenges may be related to the potential synergizing effects of various neuropeptides, e.g. CRH and vasopressin, when activating the HPA system by challenges at a suprapituitary site which may override subtle disturbances in the responsivity of the HPA system as revealed by CRH challenge alone in patients with atopic eczema.
Article
There is a large body of evidence indicating that stress influences immune competence. For example, psoriasis and atopic dermatitis may be exacerbated by psychic stress and related to abnormalities in the cellular constituents of the immune system in the skin. However, the underlying mechanisms remain unclear. We therefore investigated the potential of acute immobilization stress to affect the DTH response in BALB/c mice. DTH was significantly reduced in an immobilization time-dependent manner when stress exposure was just before sensitization. Although the number of Langerhans cells (LC) did not change under these conditions, marked alteration of LC morphology was observed with a significant decrease in area. Recovery of LC was observed within 24 h when the DTH response was also restored. Expression of the calcitonin gene-related peptide (CGRP), which inhibits LC antigen presentation, was significantly increased up to 1.6-fold in nerve fibres of immobilized mice. We conclude that stress-induced suppression of DTH could be due to reduction of LC antigen presentation with morphological change in association with CGRP elevation.
Article
When mice were subjected to restriction of movement in a small cylinder (immobilization stress), the serum interleukin (IL)-6 level rose in 1 h, following increased expression of IL-6 mRNA in both the liver and the spleen. The IL-6 mRNA induction was much greater in the liver than in the spleen when compared on a whole-organ basis. Intraperitoneal injection of bacterial lipopolysaccharide (LPS) also increased IL-6 mRNA expression in these organs, but more preferentially in the spleen. Immunohistochemical examinations of liver tissue using an antibody against murine IL-6 revealed that immobilization stress induced IL-6 mainly in hepatic parenchymal cells, whereas LPS injection did so only in sinusoidal mononuclear cells. These results indicate that immobilization stress induces IL-6 production in the liver, especially in hepatic parenchymal cells, probably by a different mechanism from that for IL-6 induction by LPS.
Article
1. Interleukin-1 receptor antagonist (IL-1Ra), as well as the interleukin-1β (IL-1β) gene response to immobilization stress (IMS), was examined in the rat brain. The reverse transcription–polymerase chain reaction was employed to determine mRNA levels. 2. IL-1β and IL-1Ra mRNA levels peaked at approximately 0.5 and 2–4 hr, respectively. The maximum mRNA levels of IL-1β were 15-fold higher than pre-IMS levels, whereas those of IL-1Ra were 250-fold higher in the hypothalamus. 3. After the biosynthesis of IL-1β has peaked, IL-1Ra may contribute to attenuation of the IL-1 activity which has been enhanced by IMS.
Article
To examine the effect of stress on skin homeostasis, cutaneous barrier recovery was measured in rate exposed to immobilization stress after tape stripping or sodium dodecyl sulphate treatment. The barrier function was evaluated by measuring transepidermal water loss. Barrier recovery was delayed in rats exposed to stress in comparison with untreated controls. This tendency was observed in both male and female animals. The delay in barrier recovery was blocked by application of the sedative drugs diazepam and chlorpromazine. The barrier recovery rate in mice which were kept at a high population density (10 animals per cage) for 2 weeks was slower than that in mice kept at lower population densities (five animals or one animal per cage). These animal models could be useful for objectively quantifying the influence of stress on the cutaneous function.
Article
The effect of the environmental pollutants, diesel exhaust particles (DEP) and formaldehyde (FA), on the production of pro-inflammatory cytokines (interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-8) by normal human dermal keratinocytes (hKCs) was investigated. Normal hKCs were incubated with various concentrations of DEP (0.4, 0.8, 4, or 20 microg/ml) or FA (0.25, 0.5, 1, or 5 microg/ml), and cytokine production was then determined by enzyme-linked immunosorbent assay (ELISA). DEP (20 microg/ml) induced IL-1beta production without altering cell growth. The increased production of IL-1beta induced by this concentration of DEP was further enhanced by the presence of phorbol 12-myristate 13-acetate (PMA), although PMA alone did not affect the levels of IL-1beta. IL-8 production was also increased by DEP (0.4 and 0.8 microg/ml), which is consistent with the results that these concentrations of DEP increased the number of cells significantly after 72 h incubation. Although FA alone did not stimulate the production of IL-1beta or IL-8 by keratinocytes, FA (0.5 microg/ml and 5 microg/ml) significantly increased IL-8 and IL-1beta production, respectively, in cells stimulated with PMA. IL-1alpha production was not modulated by FA or DEP even in the presence of PMA. TNF-alpha was produced by unstimulated keratinocytes at barely detectable levels after 48 h incubation. Although basal levels of TNF-alpha in the culture supernatants were increased after stimulation with PMA, neither pollutant alone nor combination with PMA affected the levels of TNF-alpha. These in vitro findings suggest that environmental pollutants may act as modulating factors of cutaneous inflammation by affecting the ability of keratinocytes to release pro-inflammatory cytokines.
Decrease level of ceramide in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin?
  • Imokawa
Imokawa G, Abe A, Jin K, et al. Decrease level of ceramide in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol 1991;96:523– 6.
Reduction of the DTH response is related to morphological changes of Langerhance cells in mice exposed to acute immobilization stress
  • Kawaguchi