Affiliation:
1. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
2. Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
3. State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China
Abstract
Daytime dysfunction, including symptoms like sleepiness, poor memory, and reduced responsiveness, is not well researched. It is crucial to develop animal models and study the biological mechanisms involved. We simulated sleep disorders through sleep deprivation, and stressful stimuli were used to establish daytime functional animal models. We used tests like the sodium pentobarbital sleep synergy test and the DSI telemetry system to measure sleep duration and structure. We also used tests like the Morris water maze, open field test, grip test, and baton twirling test to assess mental and physical fatigue. To assess the intrinsic biological mechanisms, we measured sleep–wake-related neurotransmitters and related receptor proteins, circadian rhythm-related proteins and cognition-related proteins in hypothalamus tissue, and oxidative stress, inflammatory factors, S100β, and HPA axis-related indexes in serum. Multi-factor sleep deprivation resulted in the disruption of sleep–wakefulness structure, memory–cognitive function degradation, decreased grip coordination, and other manifestations of decreased energetic and physical strength. The intrinsic biological mechanisms were related to the disturbed expression of sleep–wake, circadian rhythm, memory–cognition-related proteins, as well as the significant elevation of inflammatory factors, oxidative stress, the HPA axis, and other related indicators. Intrinsically related biological mechanisms and reduced sirt1 expression can lead to disruption of circadian rhythms; resulting in disruption of their sleep–wake-related neurotransmitter content and receptor expression. Meanwhile, the reduced expression of sirt1 also resulted in reduced expression of synapse-associated proteins. This study prepared an animal model of daytime dysfunction by means of multi-factor sleep deprivation. With sirt1 as a core target, the relevant biological mechanisms of neurological disorders were modulated.
Funder
special qualification for cultivating and improving the Chinese military medical service ability
National Natural Science Foundation of China
Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine
Reference37 articles.
1. Epidemiology of daytime sleepiness: Definitions, symptomatology, and prevalence;Young;J. Clin. Psychiatry,2004
2. Sleep, Cognitive impairment, and Alzheimer’s disease: A Systematic Review and Meta-Analysis;Bubu;Sleep,2017
3. Prevalence and treatment of insomnia in general practice. A longitudinal study;Hohagen;Eur. Arch. Psychiatry Clin. Neurosci.,1993
4. The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research;Buysse;Psychiatry Res.,1989
5. MRI-assessed locus coeruleus integrity is heritable and associated with multiple cognitive domains, mild cognitive impairment, and daytime dysfunction;Elman;Alzheimer’s Dement.,2021