According to a report in The American Journal of Pathology rheumatoid arthritis or RA symptoms and pathology tend to worsen in mice that lack the enzyme necessary for serotonin synthesis.
It is the first time that serotonin (5-hydroxytryptamine, 5-HT) is directly linked to the pathophysiology of RA. Despite the fact that serotonin is generally known as a neurotransmitter located in the central nervous system, research now suggest that it may have additional important functions in the periphery. A report in The American Journal of Pathology demonstrates that the effects of experimentally-induced RA in mice who suffer a serotonin deficiency tend to be worse. Furthermore, the study shows that some of the effects of RA can be reduced by serotonin or by compounds that activate serotonin receptors.
The results of the study may prove very useful for developing new treatment approaches for RA. According to co-leader investigator Marie-Christine de Vernejoul of BIOSCAR the study tends to show that serotonin has a direct immunoregulatory role in arthritis. According to her, the development of new treatments based on serotonin or serotonin receptors represents a new prospect bent on regulating the immune response in RA which can create new options when it comes to therapy for patients.
The researchers used a mouse model of RA called collagen-induced arthritis (CIA) which produces similar features to a human RA. Some of the symptoms of the disease are cartilage and bone deconstruction, and the activation of osteoclasts which are the cells responsible for bone resorption. The researchers made a comparison between the effects of CIA in normal mice and in mice genetically bred with a deficiency in tryptophan Hydroxylase-1 which is an essential enzyme required for producing serotonin in peripheral tissues.
The results of the research showed that the number and activity of osteoclasts were higher in mice with a serotonin deficiency who suffered from arthritis. Furthermore they had more bone resorption at the affected joints and at remote sites.
The mice with serotonine deficiency also suffered changes in the cytokines, which are cell-signaling molecules, in their paws. To be more precise the suffered an imbalance between T cell subtypes, especially regulatory T cells and Th17 lymphocytes.
Co-lead investigator Francine Côté of the Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications Institut Imagine stated that the mice with serotonin deficiency are characterized by an espansion of Treg associated with an enhanced shift toward a TH17 phenotype which is a situation present in patients suffering from arthritis.
The following tests with cell cultures have showed that the balance between Th17 and Treg cells could be normalized by adding 5-HT or 5-HT receptor agonist, demonstrating that serotonin has a direct regulatory role in RA.