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Prog Neuropsychopharmacol Biol Psychiatry. 2020 Mar 2;98:109818. doi: 10.1016/j.pnpbp.2019.109818. Epub 2019 Nov 16.

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

Author information

1
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
2
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
3
Department of Anatomy and Acupoint, College of Korean Medicine, Gachon University, Gyeonggi-do 13120, Republic of Korea.
4
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Anatomy & Information Sciences, Collge of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
5
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Physiology, School of Medicine, Kyung Hee University, 02447 Seoul, Republic of Korea; BioNanocomposite Research Center, Kyung Hee University, Seoul 02447, Republic of Korea.
6
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Anatomy & Information Sciences, Collge of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: acufind@khu.ac.kr.

Abstract

Clinically, it has been reported that atopic dermatitis (AD) has been linked with negative emotional problems such as depression and anxiety, thereby reducing the quality of life, but little is known about the molecular mechanism that underlies AD-associated emotional impairments. We sought to determine whether AD could induce anxiety- and depressive-like symptoms in mice and to identify pertinent signaling changes in brain reward circuitry. AD-like lesions were induced by the repeated intradermal application of MC903 into the cheek of the mouse. We assessed dermatitis severity with scratching behavior, histopathological changes, anxiety- and depressive-like behaviors using the elevated plus maze, open field and tail suspension tests, and serum corticosterone levels. In the nucleus accumbens (NAc), dorsal striatum (DS) and ventral tegmental area (VTA), protein levels of dopamine- and plasticity-related signaling molecules were determined by Western immunoblotting assay. Intradermal administration of MC903 into mouse cheek provoked a strong hind limb scratching behavior as well as the robust skin inflammation with epidermal thickening. MC903-treated mice also displayed markedly increased anxiety- and depressive-like behaviors, along with elevated serum corticosterone levels. Under these conditions, enhanced cAMP response element binding protein (CREB) and dopamine and cAMP-regulated phosphoprotein, 32 kDa (DARPP32) phosphorylation, significantly higher brain-derived neurotrophic factor (BDNF) and ΔFosB, but reduced tyrosine hydroxylase (TH) and dopamine D1 receptor (D1R) protein expression were found in the NAc, DS and VTA. Striatal BDNF, phospho-DARPP32 and phospho-CREB levels were significantly associated with the levels of depressive-like behavior in these mice. Taken together, these findings demonstrate that AD-like skin lesion elicits anxiety- and depressive-like phenotypes that are associated with neuroplasticity-related changes in reward circuitry, providing a better understanding of AD-associated emotional impairments.

KEYWORDS:

Anxiety; Atopic dermatitis; Depression; Neuronal adaptation; Pruritus

PMID:
31743694
DOI:
10.1016/j.pnpbp.2019.109818
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