Sustained neuroinflammation has been shown to be a major contributor to the progression of various neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, among others. Neuroinflammation, like other cellular processes, has been found to be influenced by circadian rhythms. Many essential elements of the brain immune system, including microglia, undergo circadian oscillations, which may play a role in the activation of inflammatory mechanisms leading to or exacerbating neuroinflammation. We have studied the complex relationships among neuroinflammation, microglia, and the circadian clock by examining the effects of various inflammatory stimuli on the microglial clock and its clock-controlled responses. We focus on understanding how the microglial clock controls pro- and anti-inflammatory responses in BV2 microglia, with special attention to the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase isoform 2 (NOX2). NOX2 activation in microglia results in the production of reactive oxygen and nitrogen species leading to increased oxidative stress, an integral characteristic of neuroinflammation. Understanding how clock genes control NOX2 activation may lead to interventional therapies to mitigate various neurodegenerative diseases associated with neuroinflammation. Along with NOX2, we have also studied the effect of the microglial circadian clock on both pro- and anti-inflammatory cytokines. We have found that various NOX2 components and cytokines are under the control of the circadian clock and display rhythmic expression. We also discovered that their oscillation is highly dependent on the inflammatory stimuli used. These findings might help bridge various gaps in our understanding of circadian control of neuroinflammation and help us attain new a perspective on tackling neuroinflammation.

Role of the circadian clock on microglial-driven neuroinflammation

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.