The effect of REV-ERBα on the inflammatory response in the 6-hydroxydopamine-injected mouse model of Parkinson’s disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease characterized by a dopaminergic (DAergic) neuronal loss in the substantia nigra pars compacta (SNpc). Neuroinflammatory response contribute to the cascade of events leading to DAergic loss. Recently, although circadian dysfunction has been proposed as one of risk factor for neuroinflammtion and neuronal loss in neurodegenerative disease, the exact role of REV-ERBα remains elusive. In the present study, we examined how REV-ERBα mediates neuroinflammation in the striatal 6-hydroxdyopamine (6-OHDA)-injected mice in heterozygous and homozygous mouse. Rev-erbα knockout (RKO) mice. RKO caused exacerbated DAergic neuronal loss according to time post injection. We aimed to observed changes in microglia (IBA-1) and astrocyte (GFAP) using immunochemistry (IHC). The number of microglia increased 2 weeks after 6-OHDA injection in SNpc and striatum. Astrocyte number also increased over time in SNpc and striatum after 6-OHDA injection. Furthermore, changes in cytokines and chemokines in microglia and astrocytes were altered based on genotype and time. In summary, we observed that Rev-erbα affects the neuroinflammation response of microglia and astrocytes in PD induced mouse model by 6-OHDA.