Rheumatoid Arthritis exposed by Serotonin levels

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Rheumatoid Arthritis exposed by Serotonin levels

In rheumatoid arthritis, a central nervous system neurotransmitter- Serotonin (5-hydroxytryptamine, 5-HT) has demostrated good results in the periphery of this disease.

According to American Journal of Pathology, additional key functions for serotonin has been inferred. Some of the effects of RA can be lowered by serotonin or its agonists. ‘The number and activity of osteoclasts, cells responsible for bone destruction were higher in serotonin deficiency.”

As a result of these findings, the new treatment approaches for RA has paved way for it's foundation. Co-lead investigator Marie-Christine de Vernejoul of BIOSCAR, France explained "Our study highlights that 5-HT has a direct immunoregulatory role in arthritis. The development of treatments targeting 5-HT or 5-HT receptors could represent an exciting prospect to regulate the immune response in RA and open new perspectives to improve the therapeutic options for patients,"

Collegen-induced arthritis (CIA) mouse model of RA used by the investigators has been constructed showing the features similar to that of human RA. The disease expressions comprise of cartilage and bone destruction, activation of osteoclasts (cells responsible for bone resorption). Deficiency in tryptophan hydroxylase-1, a key enzyme needed for serotonin production in peripheral tissues has shown the effects of CIA on comparison of normal mice and genetically bred mice. The activity and number of osteoclasts were higher in 5-HT-deficient mice with arthritis as depicted by the investigators. Also, the affected joints and remote sites showed more bone resorption.

Also, changes in cytokines (higher IL-17, higher TNF-α, and lower IL-4) - cell-signaling molecules in the paws were shown in mice with arthritis having serotonin deficiency. Clearly, they presented a shift in the balance between regulatory T cells and Th17 lymphocytes and also the T cell subtypes.

The co-lead investigator Francine, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications Institute quoted "Altogether, our data show that 5-HT deficient mice are characterized by a relative, dampened expansion of Treg associated with an enhanced shift toward a Th17 phenotype, a situation previously described in patients with arthritis,"

A direct regulatory role of serotonin in RA has been revealed from subsequent experiments using cell cultures showing balance between Th17/Treg cells which could be normalized by addition of 5-HT or 5-HT receptor agonists. Hence, a new therapeutic target that could be potent for this disabling disease has been drawn from this novel data.

Eurekalert

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