Time-of-Day-Dependent Variations of Scratching Behavior and Transepidermal Water Loss in Mice that Developed Atopic Dermatitis

Abstract

Scratching and skin barrier dysfunctions are pivotal features and therapeutic targets of atopic dermatitis (AD); however, time-of-day-dependent variations of these characteristics remain unclear. NC/Tnd mice have been shown to exhibit severe scratching behavior and skin barrier disruption together with the development of spontaneous atopic dermatitis when they are raised under air-uncontrolled environment. In the present study, time-of-day-dependent variations of scratching behavior and transepidermal water loss (TEWL) were evaluated in NC/Tnd mice that developed moderate to severe AD. Analysis of the mice for 24 hr revealed that scratching frequency and duration were increased from in the afternoon to the nocturnal period when locomotor activity was low, and scratching behavior was decreased in the morning. The highest scratching frequency and duration were 3.8- and 4.1-fold increases in the lowest scratching frequency and duration, respectively. In addition, TEWL on the dorsal skin lesion was decreased in the diurnal period, while that was increased in the nocturnal period. The highest TEWL was a 1.3-fold increase in the lowest TEWL. Significant daily variations were detected in scratching frequency and duration and TEWL. These results indicate that NC/Tnd mice are an appropriate mouse model to investigate time-of-day-dependent variations of scratching behavior and skin barrier dysfunctions associated with AD.

Can intermittent,time‐restrictedcircadian fasting modulate cutaneous severity of dermatological disorders? Insights from a multicenter, observational, prospective study

“…42 Some authors had also hypothesized that circadian rhythm alterations may lead to proinflammatory cytokine production and release, immune system triggering and skin physiology modifications, such as trans-cutaneous water loss (TEWL) and skin blood flow. [43][44][45][46] Skin barrier dysfunctions exhibit circadian variations that reflect symptoms fluctuation, especially for itch. 46 Solar light, the main driver of the circadian rhythm, is also adopted as dermatological treatment for inflammatory dermatoses with its UVA and UVB components 47,48 and demonstrates several systemic effects also in psoriasis-related comorbidities (ie, respiratory ones) 49,50 suggesting that chronomedicine may be considered an alternative approach to recondition immune system.…”

“…[43][44][45][46] Skin barrier dysfunctions exhibit circadian variations that reflect symptoms fluctuation, especially for itch. 46 Solar light, the main driver of the circadian rhythm, is also adopted as dermatological treatment for inflammatory dermatoses with its UVA and UVB components 47,48 and demonstrates several systemic effects also in psoriasis-related comorbidities (ie, respiratory ones) 49,50 suggesting that chronomedicine may be considered an alternative approach to recondition immune system. However, our study suffers from some limitations that should be acknowledged.…”

Inhibitory Effect of Valencene on the Development of Atopic Dermatitis‐Like Skin Lesions in NC/Nga Mice

“…Topical glucocorticoids (GCs) are effective anti-inflammatory drugs frequently used in the treatment of AD [ 16 , 17 ]. Despite the excellent anti-inflammatory properties of GCs, their undesirable side effects, which include cutaneous atrophy, rebound phenomenon, and decreased skin barrier function, can limit their use [ 6 ]. These limited and imperfect therapeutic options have led to substantial public interest in further drug exploration and development for AD.…”

“…Microscopically, lesional samples of AD patients also show epidermal hyperplasia, acanthosis, and accumulation of lymphocytes and mast cells [ 4 , 5 ]. Patients with AD generally suffer from severe itch, and the strong action of scratching elicits inflammation of the skin lesions, leading to more itching and exacerbating clinical signs [ 6 , 7 ]. Therefore, reducing skin inflammation is considered an effective strategy that can prevent aggravation of skin lesions and improve the quality of life for patients with AD.…”

Clockwork allergy: How the circadian clock underpins allergic reactions

“…Scratching and skin barrier dysfunction (eg, enhanced TEWL), pivotal features of AD, show circadian rhythms in patients with AD and NC/Tnd mice, an AD model. 5,36 In the epidermis of wild-type mice, expression of aquaporin 3 (Aqp3), a regulator of water content and TEWL, exhibits circadian rhythms, which become arrhythmic in Clock-mutated mice. 37 Specifically, mouse Aqp3 and the human homolog AQP3 exhibit daily oscillation in mouse skin or human keratinocytes.…”