Brain clearance is reduced during sleep and anesthesia

Miao, Andawei; Luo, Tianyuan; Hsieh, Bryan; Edge, Christopher J.; Gridley, Morgan; Wong, Ryan Tak Chun; Constandinou, Timothy G.; Wisden, William; Franks, Nicholas P.

doi:10.1038/s41593-024-01638-y

Cited by 20 publications

(2 citation statements)

References 36 publications

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“…Chronic sleep disturbances can impair the efficiency of the glymphatic system, leading to a buildup of beta-amyloid, which can further disrupt sleep, creating a vicious cycle [10]. Although recent evidence has challenged the role of sleep in clearing the extracellular space from potentially accumulating toxins [40], the evidence supporting sleep in preventing beta-amyloid accumulation remains robust [2]. Consistent with these findings, we observed that sleep enhancement via rocking reduced beta-amyloid levels in the brain.…”

Section: Discussionsupporting

confidence: 83%

Enhancing sleep via rocking ameliorates motor behavior and reduces beta-amyloid levels in a mouse model of Alzheimer’s disease

Zhang,

Santoni,

Ngo

et al. 2024

Preprint

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline and characterized by beta-amyloid plaque and tau tangle pathology. Recent research indicates a bidirectional relationship between AD pathology and sleep disturbances, with disrupted sleep exacerbating AD progression through increased beta-amyloid and tau accumulation. This strongly indicates that improving sleep may exert a direct protective effect on preventing the accumulation and spreading of AD pathology, and possibly slow the cognitive decline.Here we investigated the effects of enhancing sleep via vestibular stimulation (rocking) on AD progression in a 3xTg mouse model. Over a four-month period starting in early adulthood (p60), we monitored sleep patterns, motor function, memory, and AD pathology. Twelve-hour rocking during the light period significantly increased non-rapid eye movement (NREM) sleep duration in mice, although this effect diminished over time due to habituation. Despite this, rocking attenuated motor function decline and reduced beta-amyloid levels in the cerebral cortex of treated mice. No noticeable changes in tau levels were observed following sleep enhancement.In conclusion, our findings highlight the potential of non-pharmacological methods to enhance NREM sleep and modify disease trajectory in AD models, emphasizing the critical role of sleep in neuroprotection.

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Section: Discussionsupporting

confidence: 83%

Enhancing sleep via rocking ameliorates motor behavior and reduces beta-amyloid levels in a mouse model of Alzheimer’s disease

Zhang,

Santoni,

Ngo

et al. 2024

Preprint

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“…Additionally, risk factors that should also be taken into consideration in the binomial sleep-glymphatic system include the impact of elevated ambient temperatures, affecting not only sleep but also thermoregulation and autonomic system reactivity [20]. The convergence of evidence from animal models also demonstrated that brain clearance is reduced during sleep and in the presence of anesthetics, especially dexmedetomidine, ketamine-xylazine and pentobarbital [21]. Why this occurs remains a matter of discussion.…”

Section: The Second Question: Factors Influencing/modulating the Glym...mentioning

confidence: 99%

“Glymphatic” Neurodegeneration: Is Sleep the Missing Key?

Ferini-Strambi,

Salsone

2024

CTN

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Robust evidence suggests that the glymphatic system plays a key role in preserving brain health. Indeed, its activity in maintaining homeostasis by clearing neurotoxic proteins such as beta-amyloid from the human brain is essential. Sleep represents the factor that mainly influences this system, since it is selectively active during the night, in particular during non-rapid eye movement (NREM) sleep. This is true, since the sleep head position, in particular the supine position for its relationship to the status of opening/closing of the jugular veins, appears to be determinant for the development of future neurodegeneration. Growing evidence from human and animal models highlights the neurobiological link between sleep, glymphatic dysfunction and neurodegeneration. On the other hand, several modifiable factors have been recently identified modulating (improve/reduce) glymphatic system activity, such as Omega-3 polyunsaturated fatty acids, stress, hypertension, physical activity, alcohol, gender and genetic predisposition, in particular variants of aquaporin-4 (AQP4). From this viewpoint, our ambition is to discuss how the glymphatic system works in the brain, what factors mainly impact on this activity and its strict relation with the neurodegeneration. Future directions might include the analysis of factors modulating glymphatic system activity and a personalized glymphatic profile, “glymphatom”, as a natural target for preventive neurodegenerative treatment.

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Intersection of Sleep Disorders and Parkinson Disease: Unveiling the Bidirectional Relationship

Antelmi,

Lanza,

Mogavero

et al. 2024

Movement Disord Clin Pract

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BackgroundPatients with Parkinson's Disease (PD) frequently exhibit non‐motor symptoms, particularly sleep disturbances. Sleep disorders in PD patients are intricately linked to the pathogenesis and progression of PD itself, exacerbating neurodegenerative processes and worsening patient quality of life.ObjectivesThis review underscores the significance of sleep disorders in PD, highlighting their prevalence, impact on disease progression, and the bidirectional relationship between sleep disruption and neurodegeneration. It aims to enhance clinician awareness for better diagnosis and management of sleep‐related comorbidities in PD.MethodsA comprehensive literature search was conducted in PubMed and Scopus using key terms such as “sleep disorders”, “Parkinson's disease”, “REM sleep behavior disorder”, “restless legs syndrome”, “insomnia”, “obstructive sleep apnea”, “excessive daytime sleepiness”, “circadian rhythm disorders”, “sleep and neurodegeneration”.ResultsSleep disorders are prevalent in PD affecting up to 90% of patients. Conditions such as insomnia, REM sleep behavior disorder, restless legs syndrome, obstructive sleep apnea, excessive daytime sleepiness, and circadian rhythm disorders are commonly reported. These disorders are linked to multifactorial biological mechanisms and are associated with more severe disease phenotypes. Of note, several evidence shows that sleep abnormalities may contribute to neuroinflammation and neurodegeneration, further accelerating the disease course.ConclusionsSleep disturbances are critical non‐motor symptoms in PD. Early diagnosis and tailored management of sleep disorders are essential for improving clinical outcomes and potentially offering neuroprotective benefits.

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Brain clearance is reduced during sleep and anesthesia

Cited by 20 publications

References 36 publications

Enhancing sleep via rocking ameliorates motor behavior and reduces beta-amyloid levels in a mouse model of Alzheimer’s disease

Enhancing sleep via rocking ameliorates motor behavior and reduces beta-amyloid levels in a mouse model of Alzheimer’s disease

“Glymphatic” Neurodegeneration: Is Sleep the Missing Key?

Intersection of Sleep Disorders and Parkinson Disease: Unveiling the Bidirectional Relationship

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