WHOLE BRAIN MAPPING OF ARTHRITIS-INDUCED NEURONAL ACTIVATION

Rheumatoid arthritis (RA) is one of the most debilitating chronic human diseases and affects 1% of the world's population. Although there has been an improvement in the treatment of RA, most patients do not achieve disease remission. Therefore, there is still a need for new treatments. Recently, neuromodulation has emerged as a potential treatment approach. However, the role of brain networks controlling the onset and progression of inflammatory arthritis is completely understudied. We used activity-dependent cell labeling for mapping neuronal networks in the brain that respond to onset and progression of arthritis. We used TRAP2 mouse model, which has inducible Cre expression linked to gene c-fos, backcrossed to the Ai14 strain that expresses tdTomato fluorescence in presence of the Cre protein. We utilized the collagen antibody-induced arthritis (CAIA) model, which consists of an injection of antibodies against collagen II, and an injection of lipopolysaccharide to provide an immune trigger. Saline-injected animals were used as controls. Animals develop peak disease by day 7 with a significant increase in systemic and local cytokines. We then studied changes in the brain using serial two-photon tomography microscopy and observed significantly increased neuronal activity in different brain regions in CAIA mice: cortical areas (somatosensory and motor cortex); hippocampal regions (entorhinal cortex and dentate gyrus); striatum and pallidum (medial amygdalar nucleus and BNST); thalamic regions (PVT); hypothalamic areas (posterior hypothalamic nucleus); midbrain regions; and medullary areas(spinal trigeminal nucleus (caudal part)). In conclusion, this increased activation hint at specific brain regions being activated during the inflammatory response.