Cortical diurnal rhythms remain intact with microglial depletion

• Published in: Scientific reports 2022-01, Vol.12 (1), p.114-114, Article 114
• Main Authors: Barahona, Rocio A., Morabito, Samuel, Swarup, Vivek, Green, Kim N.
• Format: Article
• Language: English
• Subjects: 631/378/1385; 631/378/2596; Animals; Brain Waves - drug effects; Circadian Rhythm - drug effects; Circadian Rhythm - genetics; Circadian Rhythm Signaling Peptides and Proteins - genetics; Circadian Rhythm Signaling Peptides and Proteins - metabolism; Circadian rhythms; Diurnal; Extracellular matrix; Gene expression; Gene Expression Regulation; Humanities and Social Sciences; Inflammation; Male; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - metabolism; Microglia - pathology; Morphology; multidisciplinary; Nerve Net - drug effects; Nerve Net - metabolism; Nerve Net - pathology; Nerve Net - physiopathology; Organic Chemicals - pharmacology; Oscillations; Perineuronal nets; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Science; Science (multidisciplinary); Somatosensory Cortex - drug effects; Somatosensory Cortex - metabolism; Somatosensory Cortex - pathology; Somatosensory Cortex - physiopathology; Time Factors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-04079-w

Microglia are subject to change in tandem with the endogenously generated biological oscillations known as our circadian rhythm. Studies have shown microglia harbor an intrinsic molecular clock which regulates diurnal changes in morphology and influences inflammatory responses. In the adult brain, microglia play an important role in the regulation of condensed extracellular matrix structures called perineuronal nets (PNNs), and it has been suggested that PNNs are also regulated in a circadian and diurnal manner. We sought to determine whether microglia mediate the diurnal regulation of PNNs via CSF1R inhibitor dependent microglial depletion in C57BL/6J mice, and how the absence of microglia might affect cortical diurnal gene expression rhythms. While we observe diurnal differences in microglial morphology, where microglia are most ramified at the onset of the dark phase, we do not find diurnal differences in PNN intensity. However, PNN intensity increases across many brain regions in the absence of microglia, supporting a role for microglia in the regulation of PNNs. Here, we also show that cortical diurnal gene expression rhythms are intact, with no cycling gene changes without microglia. These findings demonstrate a role for microglia in the maintenance of PNNs, but not in the maintenance of diurnal rhythms.