Propofol improves sleep deprivation-induced sleep structural and cognitive deficits via upregulating the BMAL1
Huan Liu1,2,3,4,5, Chenyi Yang6, Xiaoqing Wang1,2,3,4,5
1The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
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.
Insights
Propofol administration improved cognitive function and sleep quality in rats after sleep deprivation. It reduced neuroinflammation by shifting microglia from M1 to M2 states, offering neuroprotection.
Area of Science:
- Neuroscience
- Sleep Medicine
- Pharmacology
Background:
- Sleep deprivation (SD) is a global health issue linked to cognitive impairment.
- Microglia activation and neuroinflammation are implicated in SD-induced cognitive deficits.
- Propofol has previously shown potential in mitigating SD effects.
Purpose of the Study:
- To investigate propofol's effects on sleep quality and cognitive function following 48-hour SD in rats.
- To explore the impact of propofol on neuroinflammation and circadian rhythm markers.
Main Methods:
- Rats underwent 48-hour sleep deprivation or natural sleep.
- Propofol was administered for 6 hours, followed by cognitive tests (Morris water maze, Y-maze).
- EEG/EMG, western blot, ELISA, and immunofluorescence analyzed sleep, circadian proteins (BMAL1), neurotrophic factors (BDNF), inflammatory markers (IL-6, IL-1β, Arg1, IL-10), and microglia activation.
Main Results:
- SD impaired cognitive performance and disrupted sleep architecture.
- SD led to abnormal BMAL1 expression, microglia activation, neuroinflammation, and nerve damage.
- Propofol treatment reversed cognitive deficits and sleep disturbances.
- Propofol reduced IL-1β and IL-6, increased BDNF, Arg1, and IL-10, and shifted microglia from M1 to M2 phenotype.
Conclusions:
- Propofol ameliorates SD-induced cognitive impairment and circadian rhythm disruption.
- Neuroprotection is achieved by reducing neuroinflammation and promoting a shift in microglia phenotype.
- Propofol demonstrates significant therapeutic potential for managing sleep deprivation consequences.
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