Adjuvant-induced rheumatoid arthritis in Lewis rats alters dopamine utilization and cytokine concentration in five brain regions

Abstract

Abstract Word Rheumatoid arthritis (RA) is a chronic autoimmune disease which can cause inflammation in joints, bone damage, as well as disability. A reported symptom of RA includes cognitive dysfunction. This study aimed to measure brain dopamine utilization and inflammatory markers in an adjuvant-induced Lewis Rat model of RA. Arthritic intensity was scored based on physical examination of the four paws. Twenty-eight days after the adjuvant injection, control and RA group were sacrificed and the frontal lobe of the cerebral cortex (Cx), hippocampus (Hip), hypothalamus (Hypo), amygdala (Amg), and cerebellum (Cbl) dissected using the stereotaxic atlas of Paximos and Watson as a guide. High performance liquid chromatography (HPLC) was used to analyze the concentration of dopamine, DOPAC, and homovanillic acid (HVA). Pro-inflammatory cytokines IL-1β, IL-6, and IL-23, and the anti-inflammatory IL-10 were measured by enzyme-linked immunosorbent assays (ELISA) in tissue homogenates. The results indicate RA significantly (p<0.05) decreased the dopamine content in Cbl, Amg, Hip and Cx; DOPAC significantly decreased in Amg and Cbl; HVA significantly decreased in Cbl. RA increased the concentration of pro-inflammatory cytokines and the anti-inflammatory cytokine IL-10 in the Cbl. IL-1β increased in Hyp, and Amg with a concomitant decrease in IL-10. IL-6 and IL-23 increased in Cx, Hip, Hypo, and Amg with a concomitant decrease in IL-10. This data provides evidence that adjuvant-induced RA alters the inflammation status and dopamine utilization of these brain regions. The results are useful in the development of novel drug therapies for the millions of RA patients at risk of developing mood changes, memory loss, and other cognitive deficits.