title: Effect of chronic mild stress on serotonergic markers in the skin and brain of the NC/Nga atopic-like mouse strain.
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.
authors.affiliation: Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. aram.rasul@ki.se
authors.forename: Aram
authors.initials: A
authors.lastname: Rasul
authors.forename: Husameldin
authors.initials: H
authors.lastname: El-Nour
authors.forename: Randy D
authors.initials: RD
authors.lastname: Blakely
authors.forename: Sol-Britt
authors.initials: SB
authors.lastname: Lonne-Rahm
authors.forename: Johan
authors.initials: J
authors.lastname: Forsberg
authors.forename: Björn
authors.initials: B
authors.lastname: Johansson
authors.forename: Elvar
authors.initials: E
authors.lastname: Theodorsson
authors.forename: Klas
authors.initials: K
authors.lastname: Nordlind
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000009:adverse effects / Q000276:immunology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004198:Disease Susceptibility; D005786:Gene Expression Regulation / Q000276:immunology; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013312:Stress, Physiological / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D044402:Receptor, Serotonin, 5-HT2A; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin