Reducing complement activation during sleep deprivation yields cognitive improvement by dexmedetomidine.
Qian Zhai1, Ying Zhang1, Mao Ye1
1Department of Anaesthesiology and Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
British Journal of Anaesthesia
|July 30, 2023
Summary
Sleep loss causes cognitive deficits by activating the complement pathway and eliminating synapses. Dexmedetomidine (DEX) reverses these effects, offering potential for treating sleep-related cognitive impairment.
Area of Science:
- Neuroscience
- Pharmacology
- Sleep Medicine
Background:
- Sleep loss is a significant societal issue linked to cognitive deficits.
- The precise mechanisms underlying sleep deprivation-induced cognitive impairment are not fully understood.
Purpose of the Study:
- To investigate the impact of dexmedetomidine (DEX) on cognitive decline caused by chronic sleep restriction (CSR).
- To elucidate the neuromolecular and cellular changes associated with CSR and the protective effects of DEX.
Main Methods:
- C57BL/6 mice underwent daily 20-hour chronic sleep restriction for 7 days.
- Cognitive function was assessed using Y-maze and novel object recognition tests.
- Neuromolecular and cellular changes, including microglial activation and synapse-related protein expression, were analyzed with and without DEX administration.
Main Results:
- Chronic sleep restriction (CSR) impaired learning and memory by 12-18% and increased microglial activation and complement C3 pathway signaling.
- CSR led to significant synapse elimination, evidenced by decreased synaptophysin and PSD-95 expression.
- Dexmedetomidine (DEX) activated astrocytic α2A adrenoceptors, inhibited complement C3 release, attenuated synapse elimination, and restored cognitive function.
Conclusions:
- Complement pathway activation and subsequent synapse elimination are key contributors to sleep loss-related cognitive deficits.
- Dexmedetomidine demonstrates a protective effect against sleep deprivation-induced complement activation and synapse loss.
- Dexmedetomidine shows promise in preventing cognitive deficits associated with sleep loss, meriting further investigation.
Related Concept Videos
01:13Insufficient Sleep and Sleep Deprivation
171
Insufficient sleep refers to not getting the recommended amount of sleep for optimal functioning, even if it's just slightly less than needed. Sleep insufficiency may occur due to lifestyle choices, such as staying up late for social events or work, resulting in routinely getting less sleep than required. For example, consistently sleeping 6 hours when the body needs 7-9 hours can lead to cumulative effects on health and well-being.
Sleep deprivation is a more severe form of sleep loss...
Sleep deprivation is a more severe form of sleep loss...
171
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
202
Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
202
01:19Management of Insomnia
281
The sleep cycle, an integral part of human health, consists of several stages with distinct characteristics and functions. It begins with a transition from wakefulness to sleep, known as the light sleep phase, followed by the restorative deep sleep phase, essential for physical recovery and growth. The cycle concludes with the Rapid Eye Movement (REM) phase, characterized by high brain activity and vivid dreaming. Insomnia, a prevalent sleep disorder, involves difficulty falling asleep, staying...
281
01:23Sedatives and Hypnotics: Overview
454
Sedatives are drugs that alleviate anxiety, while hypnotics induce sleep. Both classes of medication suppress neuronal activity, leading to a calming effect for sedatives and facilitating sleep for hypnotics.
Sedative-hypnotics are categorized into barbiturates, benzodiazepines (BZDs), and non-benzodiazepines or Z-drugs. These drugs work by suppressing central nervous system activity, and this suppression is dose-dependent. Older sedative medications, like barbiturates, follow a linear curve in...
Sedative-hypnotics are categorized into barbiturates, benzodiazepines (BZDs), and non-benzodiazepines or Z-drugs. These drugs work by suppressing central nervous system activity, and this suppression is dose-dependent. Older sedative medications, like barbiturates, follow a linear curve in...
454
01:14CNS Depressants: Barbiturates and Benzodiazepines
322
CNS depressants include drugs from the category of barbiturates and benzodiazepines. They are valuable medications for managing anxiety disorders and insomnia. Barbiturates, once used to induce and maintain sleep, have been replaced mainly by benzodiazepines due to barbiturate's toxicity, tolerance, and overdose risks. They interact with GABAA receptors, leading to sedation at low doses and potentially coma and death at higher doses. Phenobarbital, a long-acting barbiturate, possesses...
322
01:11Understanding Sleep
414
Sleep, an essential biological state, involves significant reductions in physical activity, sensory awareness, and interaction with the environment. This complex physiological process is primarily regulated by specific brain regions, notably the hypothalamus and pons, which govern the sleep-wake cycle or circadian rhythm.
The circadian rhythm, a nearly 24-hour cycle, is deeply influenced by environmental light cues. Light exposure directly affects the hypothalamus, which in turn regulates...
The circadian rhythm, a nearly 24-hour cycle, is deeply influenced by environmental light cues. Light exposure directly affects the hypothalamus, which in turn regulates...
414