Regional Changes in Brain Biomolecular Markers in a Collagen-Induced Arthritis Rat Model.

Simple Summary: Auto-immune disorders, such as rheumatoid arthritis, are characterized by high levels of pro-inflammatory cytokines. Continued exposure to high levels of systemic inflammation has several other health consequences, including negative effects on organs such as the brain. These detrimental effects may result in mood and neurological disorders. However, the exact mechanisms through which inflammation can result in mood disturbances and neurological disorders are not well known and are difficult to study in humans. The collagen-induced arthritis (CIA) rat model has been used to mimic human autoimmune disorders and systemic inflammation. In this study, we used the CIA model to gain a better understanding of the role of inflammation on the processes that may be involved in mood and neurological disorders, by looking at several molecular markers in different brain regions. Our results showed that all the brain regions studied in the CIA rats had high levels of local inflammation, which may have resulted in cell death in these areas. We also showed that the markers associated with neuron health and neurotransmitters implicated in mood disturbances were dysregulated in some, but not all brain regions. These results suggest that inflammation induced by autoimmune disorders may result in neuroinflammation that could result in neurodegeneration. Background: The effects of collagen-induced arthritis (CIA), a model of systemic inflammation, on brain regional molecular markers associated with neurological disorders are uncertain. Objective: This study investigated the brain regional molecular changes in markers associated with inflammation and neuronal dysfunction in a CIA model. Methods: Fourteen male Sprague Dawley rats were divided into control (n = 5) or CIA (n = 9) groups. 10 weeks after CIA induction, brain tissue was collected. Brain regional mRNA expression of inflammatory markers (IL-1β and IL-6), apoptotic markers (BAX and Bcl2) and neurotrophic factors (BDNF, CREB and TrkB) was determined. Monoamine distribution and abundance in different brain regions were determine by mass spectrometry imaging (MSI). Results: Neuroinflammation was confirmed in the CIA group by increased IL-β mRNA expression, concurrent with an increased BAX/Bcl2 ratio. The mRNA expression of CREB was increased in the midbrain and hippocampus while BDNF was increased and TrkB was decreased across all brain regions in CIA compared to control animals. Serotonin was decreased in the midbrain and hippocampus while dopamine was decreased in the striatum of CIA rats, compared to controls. Conclusion: CIA resulted in neuroinflammation concurrent with an apoptotic state and aberrant expression of neurotrophic factors and monoamines in the brain, suggestive of neurodegeneration. [ABSTRACT FROM AUTHOR]