Serotonergic mechanisms in atopic dermatitis

<p>Atopic dermatitis (AD) may be worsened by stress and anxiety. Serotonin (5-hydroxytryptamine; 5-HT) is an important mediator in stress and anxiety.</p><p>In the present thesis serotonergic mechanisms were studied in atopic dermatitis (AD). In an atopic-like mouse model, NC/Nga, that was subjected to chronic mild stress, we studied expression of serotonergic markers 5-HT1A and 5-HT2A receptors (R) and serotonin transporter protein (SERT) in skin, cerebrum and cerebellum. There was an upregulation of 5-HT1AR in the skin, cerebrum and cerebellum, during inflammation, irrespective of stress, while the 5-HT2AR was upregulated in the cerebrum, hippocampal CA1 area, and in the cerebellum, Purkinje cell layer, while being downregulated in the skin, during chronic mild stress.</p><p>In human AD patients serotonergic markers in relation to extent of the disease, pruritus, chronic stress and psychodemographic data with focus on trait anxiety and depression, were studied. We found a correlation between the extent of the disease and dermal 5-HT1AR-positive dermal inflammatory cells in the lesional skin and 5-HT2AR-positive vessels in the non-lesional skin, respectively. There was a correlation between depression with the epidermal positive 5-HT1AR fraction, while a reverse correlation with the number of 5-HT2AR expressing vessels, both in the lesional skin. In the lesional skin there was a reverse correlation for the basal SERT immunoreac-tivity with stress susceptibility.</p><p>Moreover, the effect of intradermal injection of 5-HT was studied in patients with AD and in healthy controls, on vascular response and pruritus, estimated by a computerized VAS recorder. No difference was seen regarding pruritus, while the vascular response to 5-HT was reduced in the AD patients, compared to the healthy controls.</p><h3>List of scientific papers</h3><p>I. Aram Rasul, Husameldin El-Nour, Randy D. Blakely, Sol-Britt Lonne-Rahm, Johan Forsberg, Björn Johansson, Elvar Theodorsson, Klas Nordlind.Effect of chronic mild stress on serotonergic markers in the skin and brain of the NC/Nga atopic-like mouse strain. Arch Dermatol Res. 2011; 303:625–33. <br><a href="https://doi.org/10.1007/s00403-011-1138-8">https://doi.org/10.1007/s00403-011-1138-8</a><br><br> </p><p>II. Aram Rasul, Björn Johansson, Sol-Britt Lonne-Rahm, Klas Nordlind, Elvar Theodorsson, Husameldin El-Nour. Chronic mild stress modulates the 5-HT1A and 5-HT2A receptor expression in the cerebellar cortex of NC/Nga atopic–like mice. [Submitted]</p><p>III. A. Rasul, H. El-Nour, S.B. Lonne-Rahm, O. Fransson, C. Johansson, B. Johansson, M. Zubeidi, E. Seeberg, D. Radu Djurfeldt, E.C. Azmitia, K. Nordlind. Serotonergic markers in the skin of atopic dermatitis patients in relation to chronic stress and anxiety. A correlative study. [Manuscript]</p><p>IV. Aram Rasul, Klas Nordlind and Carl-Fredrik Wahlgren. Pruritic and Vascular Responses Induced by Serotonin in Patients with Atopic Dermatitis and in Healthy Controls. Acta Derm Venereol. [Accepted] <br><a href="https://doi.org/10.2340/00015555-1473">https://doi.org/10.2340/00015555-1473</a><br><br> </p>