Huang Tianke, Zhang Xianxie, Qi Ling, Li Fang, Liu Zuoxu, Wang Zhixing, Ru Yi, Li Maoxing, Xiao Chengrong, Wang Yuguang, Ma Zengchun, Gao Yue
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Biomedicines. 2024 Sep 11;12(9):2070. doi: 10.3390/biomedicines12092070.
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.
白天功能障碍,包括嗜睡、记忆力差和反应迟钝等症状,尚未得到充分研究。开发动物模型并研究其中涉及的生物学机制至关重要。我们通过睡眠剥夺模拟睡眠障碍,并使用应激刺激建立白天功能动物模型。我们使用戊巴比妥钠睡眠协同试验和DSI遥测系统等测试来测量睡眠时间和结构。我们还使用莫里斯水迷宫、旷场试验、握力试验和转棒试验等测试来评估精神和身体疲劳。为了评估内在生物学机制,我们测量了下丘脑组织中与睡眠-觉醒相关的神经递质和相关受体蛋白、昼夜节律相关蛋白和认知相关蛋白,以及血清中的氧化应激、炎症因子、S100β和HPA轴相关指标。多因素睡眠剥夺导致睡眠-觉醒结构紊乱、记忆-认知功能退化、握力协调性下降以及其他精力和体力下降的表现。内在生物学机制与睡眠-觉醒、昼夜节律、记忆-认知相关蛋白的表达紊乱有关,以及炎症因子、氧化应激、HPA轴等相关指标的显著升高。内在相关的生物学机制和sirt1表达降低可导致昼夜节律紊乱;导致其与睡眠-觉醒相关的神经递质含量和受体表达紊乱。同时,sirt1表达降低也导致突触相关蛋白表达降低。本研究通过多因素睡眠剥夺制备了白天功能障碍动物模型。以sirt1为核心靶点,调节神经疾病的相关生物学机制。