Propofol improves sleep deprivation‐induced sleep structural and cognitive deficits via upregulating the BMAL1 expression and suppressing microglial M1 polarization

Abstract

Background

Sleep deprivation (SD) is a growing global health problem with many deleterious effects, such as cognitive impairment. Microglia activation‐induced neuroinflammation may be an essential factor in this. Propofol has been shown to clear sleep debt after SD in rats. This study aims to evaluate the effects of propofol‐induced sleep on ameliorating sleep quality impairment and cognitive decline after 48 h SD.

Methods

Almost 8–12‐week‐old rats were placed in the SD system for 48 h of natural sleep or continuous SD. Afterwards, rats received propofol (20 mg·kg ⁻¹·h ⁻¹, 6 h) via the tail or slept naturally. The Morris water maze (MWM) and Y‐maze test assessed spatial learning and memory abilities. Rat EEG/EMG monitored sleep. The expression of brain and muscle Arnt‐like protein 1 (BMAL1), brain‐derived neurotrophic factor (BDNF) in the hippocampus and BMAL1 in the hypothalamus were assessed by western blot. Enzyme‐linked immunosorbent assay detected IL‐6, IL‐1β, arginase 1 (Arg1), and IL‐10 levels in the hippocampus. Immunofluorescence was used to determine microglia expression as well as morphological changes.

Results

Compared to the control group, the sleep‐deprived rats showed poor cognitive performance on both the MWM test and the Y‐maze test, accompanied by disturbances in sleep structure, including increased total sleep time, and increased time spent and delta power in non‐rapid eye movement sleep. In addition, SD induces abnormal expression of the circadian rhythm protein BMAL1, activates microglia, and causes neuroinflammation and nerve damage. Propofol reversed these changes and saved sleep and cognitive impairment. Furthermore, propofol treatment significantly reduced hippocampal IL‐1β and IL‐6 levels, increased BDNF, Arg1, and IL‐10 levels, and switched microglia surface markers from the inflammatory M1 type to the anti‐inflammatory M2 type.

Conclusion

Propofol reduces SD‐induced cognitive impairment and circadian rhythm disruption, possibly by lowering neuronal inflammation and switching the microglia phenotype from an M1 to an M2 activated state, thus exerting neuroprotective effects.

Abstract

Acute sleep deprivation leads to cognitive deficits and disturbances in sleep structure, which are associated with microglia activation. Propofol works by inhibiting microglia, promoting the conversion of M1 to M2, reducing neuroinflammation, improving sleep quality, and reversing the cognitive deficits caused by sleep deprivation.