Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation.

Serotonin (5-hydroxytryptamine, 5-HT) is a well-known neurotransmitter that is involved in a growing number of functions in peripheral tissues. Recent studies have shown nonpharmacological functions of 5-HT linked to its chemical properties. Indeed, it was reported that 5-HT may, on the one hand, bind lipid membranes and, on the other hand, protect red blood cells through a mechanism independent of its specific receptors. To better understand these underevaluated properties of 5-HT, we combined biochemical, biophysical, and molecular dynamics simulations approaches to characterize, at the molecular level, the antioxidant capacity of 5-HT and its interaction with lipid membranes. To do so, 5-HT was added to red blood cells and lipid membranes bearing different degrees of unsaturation. Our results demonstrate that 5-HT acts as a potent antioxidant and binds with a superior affinity to lipids with unsaturation on both alkyl chains. We show that 5-HT locates at the hydrophobic-hydrophilic interface, below the glycerol group. This interfacial location is stabilized by hydrogen bonds between the 5-HT hydroxyl group and lipid headgroups and allows 5-HT to intercept reactive oxygen species, preventing membrane oxidation. Experimental and molecular dynamics simulations using membrane enriched with oxidized lipids converge to further reveal that 5-HT contributes to the termination of lipid peroxidation by direct interaction with active groups of these lipids and could also contribute to limit the production of new radicals. Taken together, our results identify 5-HT as a potent inhibitor of lipid peroxidation and offer a different perspective on the role of this pleiotropic molecule.

Serotonin and orthodontic tooth movement.

Peripheral serotonin continuously reveals its unexpected involvements in many organ functions. In bone tissue, there is an increasing evidence for a local serotonergic system affecting the cellular and molecular actors involved in bone turnover. During orthodontic treatment, tooth movement relies on bone remodeling, itself a result of the inflammatory process triggered by application of orthodontic forces to the teeth. Nowadays, many adults proceed to an orthodontic treatment, it therefore seems important to consider physiological growth-related factors and external factors as medications that may influence adverse effects and efficacy of orthodontic treatment techniques. In this review, we focus on peripheral serotonin mechanism of regulation of bone remodeling during orthodontic movement. We discuss the differential effect of serotonin on alveolar bone inflammation that may open new strategies in orthodontics.