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Updated: Jun 21, 2025
Light/dark Transition Test for Mice
Published on: November 13, 2006
Microglia undergo molecular and functional adaptations to dark and light phases in male laboratory mice
Daniele Mattei1, Andranik Ivanov2, Jacqueline Hammer3
1Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, 8057 Zurich, Switzerland; Nash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Abstract:
Microglia are increasingly recognized to contribute to brain health and disease. Preclinical studies using laboratory rodents are essential to advance our understanding of the physiological and pathophysiological roles of these cells in the central nervous system. Rodents are nocturnal animals, and they are mostly maintained in a defined light-dark cycle within animal facilities, with many laboratories investigating the molecular and functional profiles of microglia exclusively during the animals' light (sleep) phase. However, only a few studies have considered possible differences in microglial functions between the active and sleep phases. Based on initial evidence suggesting that microglial intrinsic clock genes can affect their phenotypes, we sought to investigate differences in transcriptional, proteotype and functional profiles of microglia between light (sleep) and dark (active) phases, and how these changes are affected in pathological models. We found marked transcriptional and proteotype differences between microglia harvested from male mice during the light or dark phase. Amongst others, these differences related to genes and proteins associated with immune responses, motility, and phagocytosis, which were reflected by functional alterations in microglial synaptic pruning and response to bacterial stimuli. Possibly accounting for such changes, we found RNA and protein regulation in SWI/SNF and NuRD chromatin remodeling complexes between light and dark phases. Importantly, we also show that the time of microglial sample collection influences the nature of microglial transcriptomic changes in a model of immune-mediated neurodevelopmental disorders. Our findings emphasize the importance of considering diurnal factors in studying microglial cells and indicate that implementing a circadian perspective is pivotal for advancing our understanding of their physiological and pathophysiological roles in brain health and disease.
Insights
Microglia exhibit distinct transcriptional and functional profiles between sleep and active phases in mice. Understanding these diurnal differences is crucial for studying brain health and neurodevelopmental disorders.
Area of Science:
- Neuroscience
- Immunology
- Chronobiology
Background:
- Microglia, the central nervous system's immune cells, play roles in brain health and disease.
- Rodent models are vital for studying microglia, but often overlook diurnal variations in their function.
- Previous research suggests microglial clock genes influence their phenotypes.
Purpose of the Study:
- To investigate differences in microglial transcriptional, proteomic, and functional profiles between light (sleep) and dark (active) phases.
- To determine how these diurnal changes are affected in pathological models.
- To explore the underlying molecular mechanisms, including chromatin remodeling.
Main Methods:
- Transcriptomic and proteomic analyses of microglia from male mice during light and dark phases.
- Functional assays assessing microglial synaptic pruning and response to bacterial stimuli.
- Analysis of chromatin remodeling complexes (SWI/SNF, NuRD) in microglia.
Main Results:
- Significant transcriptional and proteomic differences were observed between light and dark phase microglia.
- Functional alterations in synaptic pruning and bacterial response correlated with these molecular changes.
- Diurnal timing of sample collection impacted microglial transcriptomic changes in a neurodevelopmental disorder model.
Conclusions:
- Microglial function exhibits significant diurnal variation, impacting their roles in brain health and disease.
- Circadian rhythms are a critical factor to consider in microglial research.
- Future studies should incorporate diurnal considerations for accurate physiological and pathophysiological assessments.
