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Effect of chronic mild stress on serotonergic markers in the skin and brain of the NC/Nga atopic-like mouse strain

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Abstract

Atopic eczema is often worsened by stress. While acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT), chronic stress causes a decrease. In chronic stress, there is a decrease of the 5-HT1A receptor (R)- and an increase in the 5-HT2AR-responsiveness to 5-HT. In the present study, the impact of chronic mild stress on the expression of 5-HT1A and 5-HT2A receptors and serotonin transporter protein (SERT) was investigated in eczematous skin and brain of atopic-like NC/Nga mice. Twenty-four NC/Nga mice were subjected to chronic mild stress for 12 weeks, and eczema was induced by applying a mite antigen (Dermatophagoides pteronyssinus) on the ears for the last 4 weeks. The mice were divided into three groups, eight per group, stressed eczematous (SE), non-stressed eczematous (NSE) and stressed control (SC). The biopsies were analysed by immunohistochemistry, using a streptavidin–biotin technique. There was an increased number of 5-HT containing dermal mast cell-like mononuclear cells in the skin of mice with eczema (SE and NSE, respectively) compared with the SC, and a tendency to more 5-HT-positive cells in the SE compared with the NSE group. Increased 5-HT1AR immunoreactivity (IR) in the skin and hippocampus of the eczematous groups compared to the control group was seen, but no difference between the SE and NSE groups. The epidermal immunoreactivity for 5-HT2AR was highest in the SE and NSE compared to the SC group, and was also higher in the SE compared to NSE. 5-HT2AR expression was also seen on nerve bundles, the number and intensity of such bundles being decreased in the SE compared to the NSE group. In the CA1 area of the hippocampus, there was an increase in the quantity of cells immunoreactive for 5-HT2AR in the SE versus the NSE group and also in the SE versus the SC group. SERT-IR was found also on nerve bundles with a decreased number in the SE compared to the NSE and SC group. There is a modulation of the expression of serotonergic markers in the eczematous skin and brain of the atopic-like mouse during chronic mild stress.

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Acknowledgments

This study was supported by a grant from the Welander/Finsen foundation. Dr. Aram Rasul is supported by the Ministry of Higher Education in Kurdistan, Iraq. The technical assistance of Anna-Lena Kastman and Eva Lindqvist is gratefully acknowledged as is the efforts of Qiao Han in SERT antibody production. We are thankful to Prof. Lars Olson, Department of Neuroscience, Karolinska Institutet, for valuable comments during the preparation of the manuscript.

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Authors and Affiliations

  1. Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

    Aram Rasul, Husameldin El-Nour, Sol-Britt Lonne-Rahm, Johan Forsberg & Klas Nordlind

  2. Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN, USA

    Randy D. Blakely

  3. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Björn Johansson

  4. IBK/Clinical Chemistry, University Hospital, Linköping, Sweden

    Elvar Theodorsson

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  1. Aram Rasul
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  2. Husameldin El-Nour
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Correspondence to Aram Rasul.

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Rasul, A., El-Nour, H., Blakely, R.D. et al. Effect of chronic mild stress on serotonergic markers in the skin and brain of the NC/Nga atopic-like mouse strain. Arch Dermatol Res 303, 625–633 (2011). https://doi.org/10.1007/s00403-011-1138-8

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  • DOI: https://doi.org/10.1007/s00403-011-1138-8

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