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The Use of Mouse Splenocytes to Assess Pathogen-associated Molecular Pattern Influence on Clock Gene Expression
Published on: July 24, 2018
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Microglia inflammatory responses are controlled by an intrinsic circadian clock
Laura K Fonken1, Matthew G Frank1, Meagan M Kitt1
1Department of Psychology and Neuroscience, University of Colorado, Boulder, CO 80309, USA.
Brain, Behavior, and Immunity
|November 30, 2014
Summary
Microglia, the brain's immune cells, have a daily rhythm influencing their inflammatory response. This circadian clock in microglia means the timing of immune challenges, like lipopolysaccharide (LPS), affects sickness behaviors and cytokine production.
Area of Science:
- Neuroimmunology
- Chronobiology
- Molecular Biology
Background:
- The circadian system regulates physiological processes, including immune responses.
- Diurnal variations in inflammatory responses to challenges like lipopolysaccharide (LPS) are known, but cellular mechanisms are unclear.
- Microglia are key immune cells in the central nervous system (CNS) and may mediate these time-dependent effects.
Purpose of the Study:
- To investigate diurnal differences in neuroinflammatory responses to LPS.
- To determine if microglia exhibit temporal variations in inflammatory factor expression.
- To explore the role of microglia's intrinsic circadian clock in mediating sickness responses.
Main Methods:
- Adult male Sprague-Dawley rats were injected with a sub-septic dose of LPS during light and dark phases.
- Hippocampal microglia were isolated, and expression of inflammatory factors and circadian clock genes was analyzed.
- Ex vivo LPS and corticosterone treatments were applied to isolated microglia.
- Microglia from adrenalectomized rats were also studied to assess glucocorticoid influence.
Main Results:
- Rats injected with LPS during the light phase showed increased sickness behaviors and hippocampal cytokine production.
- Isolated microglia rhythmically expressed inflammatory factors (TNFα, IL1β, IL6) and clock genes, peaking during the light phase.
- Light phase-isolated microglia exhibited exaggerated cytokine responses to ex vivo LPS stimulation.
- Microglia from adrenalectomized rats retained temporal differences in gene expression, suggesting glucocorticoid-independent entrainment.
Conclusions:
- Microglia possess an intrinsic circadian clock that modulates their inflammatory response.
- Time-of-day significantly influences neuroinflammatory reactions mediated by microglia.
- These findings highlight the importance of considering circadian rhythms in the timing of inflammatory interventions, such as surgeries or immunotherapies.
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