Serotonergic Mechanisms in Atopic Dermatitis

Atopic dermatitis (AD) may be worsened by stress and anxiety. Serotonin (5hydroxytryptamine; 5-HT) is an important mediator in stress and anxiety. 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. 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 5HT2AR-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 immunoreactivity with stress susceptibility. 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. 5-HT seems to have a role in AD. LIST OF PUBLICATIONS I. Aram Rasul, Husameldin El-Nour, Randy D. Blakely, Sol-Britt LonneRahm, Johan Forsberg, Björn Johansson, Elvar Theodorsson, Klas Nordlind. Effects of chronic mild stress on the expression of serotonergic markers in the skin and brain of the atopic-like mouse strain. Arch Dermatol Res 2011; 303:625–633. 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. In revision. 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. In manuscript. 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 DermVenereol (Stockh), in press.