TY - JOUR
T1 - Microglia modulate sleep/wakefulness under baseline conditions and under acute social defeat stress in adult mice
AU - Miyanishi, Kazuya
AU - Hotta-Hirashima, Noriko
AU - Miyoshi, Chika
AU - Hayakawa, Satsuki
AU - Kakizaki, Miyo
AU - Kanno, Satomi
AU - Ikkyu, Aya
AU - Funato, Hiromasa
AU - Yanagisawa, Masashi
N1 - Publisher Copyright:
© 2023
PY - 2024/5
Y1 - 2024/5
N2 - Although sleep is tightly regulated by multiple neuronal circuits in the brain, nonneuronal cells such as glial cells have been increasingly recognized as crucial sleep regulators. Recent studies have shown that microglia may act to maintain wakefulness. Here, we investigated the possible involvement of microglia in the regulation of sleep quantity and quality under baseline and stress conditions through electroencephalography (EEG)/electromyography (EMG) recordings, and by employing pharmacological methods to eliminate microglial cells in the adult mouse brain. We found that severe microglial depletion induced by the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX5622 (PLX) reversibly decreased the total wake time and the wake episode duration and increased the EEG slow-wave power during wakefulness under baseline conditions. To examine the role of microglia in sleep/wake regulation under mental stress, we used the acute social defeat stress (ASDS) paradigm, an ethological model for psychosocial stress. Sleep analysis under ASDS revealed that microglial depletion exacerbated the stress-induced decrease in the total wake time and increase in anxiety-like behaviors in the open field test. These results demonstrate that microglia actively modulate sleep quantity and architecture under both baseline and stress conditions. Our findings suggest that microglia may potentially provide resilience against acute psychosocial stress by regulating restorative sleep.
AB - Although sleep is tightly regulated by multiple neuronal circuits in the brain, nonneuronal cells such as glial cells have been increasingly recognized as crucial sleep regulators. Recent studies have shown that microglia may act to maintain wakefulness. Here, we investigated the possible involvement of microglia in the regulation of sleep quantity and quality under baseline and stress conditions through electroencephalography (EEG)/electromyography (EMG) recordings, and by employing pharmacological methods to eliminate microglial cells in the adult mouse brain. We found that severe microglial depletion induced by the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX5622 (PLX) reversibly decreased the total wake time and the wake episode duration and increased the EEG slow-wave power during wakefulness under baseline conditions. To examine the role of microglia in sleep/wake regulation under mental stress, we used the acute social defeat stress (ASDS) paradigm, an ethological model for psychosocial stress. Sleep analysis under ASDS revealed that microglial depletion exacerbated the stress-induced decrease in the total wake time and increase in anxiety-like behaviors in the open field test. These results demonstrate that microglia actively modulate sleep quantity and architecture under both baseline and stress conditions. Our findings suggest that microglia may potentially provide resilience against acute psychosocial stress by regulating restorative sleep.
KW - Anxiety-like behavior
KW - CSF1-CSF1R signalling
KW - Microglia
KW - Restorative sleep
KW - Sleep/wakefulness
KW - Social defeat stress
UR - http://www.scopus.com/inward/record.url?scp=85178590144&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85178590144&partnerID=8YFLogxK
U2 - 10.1016/j.neures.2023.11.010
DO - 10.1016/j.neures.2023.11.010
M3 - Article
C2 - 38029860
AN - SCOPUS:85178590144
SN - 0168-0102
VL - 202
SP - 8
EP - 19
JO - Neuroscience Research
JF - Neuroscience Research
ER -