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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.

In addition to the well-known motor control, the cerebellum has recently been implicated in memory, cognition, addiction, and social behavior. Given that the cerebellum contains more neurons than the cerebral cortex and has tight connections to the thalamus and brainstem nuclei, it is possible that the cerebellum also regulates sleep/wakefulness. However, the role of the cerebellum in sleep was unclear, since cerebellar lesion studies inevitably involved massive inflammation in the adjacent brainstem, and sleep changes in lesion studies were not consistent with each other. Here, we examine the role of the cerebellum in sleep and wakefulness using mesencephalon- and rhombomere 1-specific Ptf1a conditional knockout (Ptf1a cKO) mice, which lack the cerebellar cortex and its related structures, and exhibit ataxic gait. Ptf1a cKO mice had similar wake and non-rapid eye movement sleep (NREMS) time as control mice and showed reduced slow wave activity during wakefulness, NREMS and REMS. Ptf1a cKO mice showed a decrease in REMS time during the light phase and had increased NREMS delta power in response to 6 h of sleep deprivation, as did control mice. Ptf1a cKO mice also had similar numbers of sleep spindles and fear memories as control mice. Thus, the cerebellum does not appear to play a major role in sleep-wake control, but may be involved in the generation of slow waves.

Physical exercise is one of the best interventions for improving traumatic brain injury (TBI) outcomes. However, an argument has been raised regarding the timing at which physical exercise should be initiated. In this study, male Wistar rats were subjected to stab wounding of the right hemisphere to develop a TBI model and were forced to walk once on a treadmill at a 5-m/min pace at 24 h or 48 h after TBI for 10 min. Injured brain tissue was dissected after TBI to evaluate the effects of exercise. Behavioral abnormalities and motor impairment were assessed by various behavioral tests between 2 and 3 weeks after TBI. Exercise did not affect the circulating corticosterone levels and the weight of the adrenal glands. Exercise particularly that at 24 h, worsened the motor impairment of the left forelimbs. Quantitative reverse-transcription polymerase chain reaction showed that exercise at 24 h increased proinflammatory cytokines and chemokines on the third day while suppressing the proinflammatory reactions on the fourth day. Exercise at both time points decreased expression of transforming growth factor (TGF) β1 and its receptor TGFβR1. Exercise at 24 h increased phosphorylation of IκB kinase on the fourth day, which may be correlated with the decreased effects of TGFβ1. Even a low-intensity exercise activity could cause deleterious effects when it is initiated within 48 h after the onset of severe TBI, probably because of the resulting proinflammatory effects. Therefore, rehabilitation exercise programs should be initiated after 48 h of TBI onset. Keywords: Cylinder test, Beam test, IL-1β, CCL2, TGF β, IL-6