P20 Characterizing monoamine signalling in human dermal fibroblasts and keratinocytes

Abstract Introduction and aims Our mental health depends upon a fine balance of monoamines in the brain. Interestingly, there is ample evidence indicating that mental health disorders such as stress or anxiety have an impact on skin condition and appearance. For example, stress induces neurogenic inflammation, which in turn leads to mast cell degranulation in the skin and increases local histamine levels. This increased histamine within the skin exacerbates skin conditions such as eczema and psoriasis, while impacting the skin barrier. In this study, we first sought to investigate monoamine signalling in both skin keratinocytes and fibroblasts, with a specific focus on histamine and serotonin modulation. Next, we investigated mechanisms of release via pharmacological intervention to block corresponding receptors, informed by using single-cell RNA sequencing from existing datasets. Methods We adapted a powerful electrochemical technique, fast-scan cyclic voltammetry (FSCV) to codetect monoamine signalling in real-time in vitro. Employing the advanced capabilities of our artificial neural network models, we analysed extensive FSCV colour plot data in real-time to establish neurotransmitter release patterns and understand their characteristics. Results Our Results show that both keratinocytes and fibroblasts are capable of releasing serotonin and histamine without external intervention. After administering diphenhydramine, an H1 receptor inhibitor, to the cells, we observed a rise in the frequency and amplitude of both serotonin and histamine signalling compared with the cells that received no treatment. However, bafilomycin, a vacuolar H+ ATPase inhibitor, reduced the signalling frequency significantly. This suggests a potential autoregulation mechanism and interdependency between the two monoamines. Conclusions Overall, using analytical Methods, our work shows that skin-resident fibroblasts and keratinocytes can release monoamines including serotonin and histamine. This finding provides an opportunity to examine interventions that facilitate serotonin release, to decrease histamine levels, and improve the skin function and general mental wellbeing.