Atopic dermatitis induces anxiety- and depressive-like behaviors with concomitant neuronal adaptations in brain reward circuits in mice

Yeom, Mijung; Ahn, Sora; Oh, Ju-Young; Kim, Song-Yi; Lee, Hyangsook; Hahm, Dae‐Hyun; Park, Hi-Joon

doi:10.1016/j.pnpbp.2019.109818

Cited by 31 publications

(23 citation statements)

References 38 publications

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“…Yeom et al [ 49 ] hypothesized that in a mouse model of AD induced by repeated intradermal application of MC903, a synthetic vitamin D 3 analog, the anxiety- and depression-like symptoms were associated with changes in the brain reward dopaminergic circuitry, and increased plasma corticosterone levels ( Table 1 ). Striatal BDNF, phospho-DARPP32, and phospho-CREB levels emerged as biological factors significantly associated with the severity of depressive-like behavior in mice.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the increased concentration of BDNF in AD appeared to belong to a framework of an altered neuroimmune regulatory system associated with an anxiogenic-like phenotype. Yeom et al [ 49 ] hypothesized that the increased striatal BDNF concentration, along with phospho-DARPP32 and phospho-CREB, in a mouse AD model, was associated with the depressive-like behavior and increased activity of the dopaminergic reward circuitry, which is central in mediating anxiety, depression, and stress ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

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A systematic review on shared biological mechanisms of depression and anxiety in comorbidity with psoriasis, atopic dermatitis, and hidradenitis suppurativa

et al. 2021

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Background Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients’ quality of life. We hypothesized the comorbidity of depression, anxiety syndromes, or symptoms as attributable to biological mechanisms that the combined diseases share. Methods We conducted a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement searching into PubMed, PsycInfo, and Scopus databases. We examined the literature regarding the comorbidity of psoriasis (Ps), atopic dermatitis (AD), or hidradenitis suppurativa with depression and/or anxiety in adults ≥18 years and the hypothetical shared underlying biological mechanisms. Results Sixteen studies were analyzed, mostly regarding Ps and AD. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling and nuclear factor kappa-light-chain-enhancer of activated B cells/p38 mitogen-activated protein kinase pathways arose as shared mechanisms in Ps animal models with depression- and/or anxiety-like behaviors. Activated microglia and neuroinflammatory responses emerged in AD depressive models. As to genetic studies, atopic-dermatitis patients with comorbid anxiety traits carried the short variant of serotonin transporter and a polymorphism of the human translocator protein gene. A GA genotype of catechol-O-methyltransferase gene was instead associated with Ps. Reduced natural killer cell activity, IL-4, serotonin serum levels, and increased plasma cortisol and IgE levels were hypothesized in comorbid depressive AD patients. In Ps patients with comorbid depression, high serum concentrations of IL-6 and IL-18, as well as IL-17A, were presumed to act as shared inflammatory mechanisms. Conclusions Further studies should investigate mental disorders and chronic skin diseases concurrently across patients’ life course and identify their temporal relation and biological correlates. Future research should also identify biological characteristics of individuals at high risk of the comorbid disorders and associated complications.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A systematic review on shared biological mechanisms of depression and anxiety in comorbidity with psoriasis, atopic dermatitis, and hidradenitis suppurativa

et al. 2021

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“…4,54 In addition, the presence of chronic pruritic skin inflammation as such constitutes a major source of chronic perceived stress and may induce brain neuroinflammation and depressive symptoms. 55 While imitating all the highly characteristic "neurodermatitis" aspects of AD in an animal model may not be possible, at least some degree of mimicry is clearly achievable in mice: these can easily be exposed to perceived stress 56 and/or to classical mediators of perceived stress that induce mast-cell degranulation and activation in human skin (e.g. CRH, substance P 57 ) so as to assess how this impacts the development of AD-like skin lesions; also measuring changes in intracutaneous BAR2 expression levels immunohistologically is relatively simple.…”

Section: Neurophysiological Abnormalities and Neurogenic Skin Inflamentioning

confidence: 99%

“…Human AD is also associated with abnormalities in neuroendocrine stress responses such as blunted cortisol release in response to psychoemotional stressors and excessive CRH‐mediated signalling 4,54 . In addition, the presence of chronic pruritic skin inflammation as such constitutes a major source of chronic perceived stress and may induce brain neuroinflammation and depressive symptoms 55 …”

Section: The Challenge: Mimicking Key Features Of Human Admentioning

confidence: 99%

Mouse models of atopic dermatitis: a critical reappraisal

Gilhar

Reich

Keren

et al. 2021

Experimental Dermatology

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Mouse models for atopic dermatitis (AD) are an indispensable preclinical research tool for testing new candidate AD therapeutics and for interrogating AD pathobiology in vivo. In this Viewpoint, we delineate why, unfortunately, none of the currently available so-called "AD" mouse models satisfactorily reflect the clinical complexity of human AD, but imitate more "allergic" or "irriant" contact dermatitis conditions. This limits the predictive value of AD models for clinical outcomes of new tested candidate AD therapeutics and the instructiveness of mouse models for human AD pathophysiology research. Here, we propose to initiate a rational debate on the minimal criteria that a mouse model should meet in order to be considered relevant for human AD. We

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“…Recently, AD was shown to be not only a skin disease but also that affects the function of other organs. 54,55) Conversely, other organs could also affect the magnitude of AD. 56) These findings led us to hypothesize that AD in the skin and in other organs can affect each other in terms of magnitude of function/dysfunction or symptoms.…”

Section: Discussionmentioning

confidence: 99%

Methionine is a Key Regulator in the Onset of Atopic Dermatitis in NC/Nga Mice

et al. 2021

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Atopic dermatitis (AD) is a skin disorder that presents with itching and scratching and frequently progresses to a chronic state. AD often develops in patients with an individual or family history of allergic diseases. In addition, AD may develop in patients exposed to environmental stimuli such as air pollutants or dust. However, there can be differences in the magnitude of symptoms between patients even with the same genetic background or exposure to similar environmental conditions. NC/Nga mice have been used as a model for AD. They show AD-like symptoms in an age-dependent manner, even in the absence of AD-inducing agents. In addition, similar to humans, the magnitude of AD symptoms in this model varies between individual mice. However, the mechanisms underlying these differences are unclear. In addition, little is known about the relationship between AD skin symptoms and other organs and tissues. Here, we performed a metabolome analysis on sera from NC/ Nga mice to identify factors potentially related to the severity of AD symptoms. The analysis showed a correlation between reduced serum methionine levels and increased severity of AD. In addition, treatment with excess methionine before the onset of AD symptoms suppressed the development of AD. In contrast, administration of methionine after the onset of AD symptoms did not. Importantly, cysteine and taurine, irreversible metabolites of methionine, did not suppress AD development. These results show that methionine, but not its metabolites, is a key factor in the onset, rather than the development of AD.

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Atopic dermatitis induces anxiety- and depressive-like behaviors with concomitant neuronal adaptations in brain reward circuits in mice

Cited by 31 publications

References 38 publications

A systematic review on shared biological mechanisms of depression and anxiety in comorbidity with psoriasis, atopic dermatitis, and hidradenitis suppurativa

A systematic review on shared biological mechanisms of depression and anxiety in comorbidity with psoriasis, atopic dermatitis, and hidradenitis suppurativa

Mouse models of atopic dermatitis: a critical reappraisal

Methionine is a Key Regulator in the Onset of Atopic Dermatitis in NC/Nga Mice

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