The Circadian Clock of Polarized Microglia and Its Interaction with Mouse Brain Oscillators

0570554 - FGÚ 2024 RIV US eng J - Journal Article
Honzlová, Petra - Semenovykh, Kateryna - Sumová, Alena
The Circadian Clock of Polarized Microglia and Its Interaction with Mouse Brain Oscillators.
Cellular and Molecular Neurobiology. Roč. 43, č. 3 (2023), s. 1319-1333. ISSN 0272-4340. E-ISSN 1573-6830
Institutional support: RVO:67985823
Keywords : microglia * polarization * circadian clock * suprachiasmatic nuclei * mPER2Luc mouse * PLX3397
OECD category: Physiology (including cytology)
Impact factor: 4, year: 2022
Method of publishing: Limited access
https://doi.org/10.1007/s10571-022-01252-1

The activity of the immune system is controlled by circadian clocks present in different immune cells. The brain-resident subtype of immune cells, microglia, exhibits a wide range of functional phenotypes depending on the signaling molecules in their microenvironment. The exact role of microglia in the hypothalamic suprachiasmatic nuclei (SCN), the central circadian clock, has not been known. Therefore, the aim of this study was to determine (1) whether microenvironment-induced changes in microglial polarization affect circadian clocks in these cells and (2) whether the presence of microglia contributes to SCN clock function. Microglial and SCN clocks were monitored using PER2-driven bioluminescence rhythms at the tissue and single-cell levels. We found that polarization of resting microglia to a pro-inflammatory (M1) or anti-inflammatory (M2) state significantly altered the period and amplitude of their molecular circadian clock, importantly, the parameters changed plastically with the repolarization of microglia. This effect was reflected in specific modulations of the expression profiles of individual clock genes in the polarized microglia. Depletion of microglia significantly reduced the amplitude of the SCN clock, and co-cultivation of the SCN explants with M2-polarized microglia specifically improved the amplitude of the SCN clock. These results demonstrate that the presence of M2-polarized microglia has beneficial effects on SCN clock function. Our results provide new insight into the mutual interaction between immune and circadian systems in the brain.
Permanent Link: https://hdl.handle.net/11104/0341856