Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.
Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, 030001, China.
Behav Brain Res. 2021 Aug 27;412:113400. doi: 10.1016/j.bbr.2021.113400. Epub 2021 Jun 2.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits. Sleep deprivation (SD) could lead to memory deficits, and it was a candidate risk factor for AD. However, the effects of chronic SD on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1 transgenic mice and wild type (WT) littermates were subjected to chronic SD by using the modified multiple platform method (MMPM), with 20 h of SD each day for 21 days. Then, the effects of chronic SD on cognitive functions in APP/PS1 mice were tested by using behavioral tests, the potential mechanisms were investigated by in vivo electrophysiological recording, western blot and immunochemistry. The results showed that chronic SD obviously aggravated the cognitive impairments, exacerbated in vivo hippocampal long-term potentiation (LTP) suppression, reduced the expression level of PSD95, increased amyloid-β (Aβ) protein deposition and overactivated microglia in the hippocampus of APP/PS1 mice. These results indicate that chronic SD exacerbates the cognitive deficits in APP/PS1 mice by accelerating the development of AD pathologies, reducing the expression of PSD95 and aggravating the LTP suppression in hippocampus. At the same time, chronic SD also impaired cognitive functions and synaptic plasticity in WT mice through down-regulating the level of PSD95 and activating microglia. These findings further clarify the electrophysiological and molecular mechanisms of exacerbated cognitive deficits in AD caused by chronic SD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是认知功能障碍。睡眠剥夺（SD）可导致记忆缺失，并且是 AD 的候选风险因素。然而，慢性 SD 对 AD 模型小鼠认知功能的影响及其可能的机制尚不清楚。在本研究中，使用改良的多平台方法（MMPM）对 8 月龄雄性 APP/PS1 转基因小鼠和野生型（WT）同窝仔鼠进行慢性 SD，每天剥夺 20 小时，共 21 天。然后，通过行为测试测试慢性 SD 对 APP/PS1 小鼠认知功能的影响，通过体内电生理记录、Western blot 和免疫化学方法研究潜在机制。结果表明，慢性 SD 明显加重了认知障碍，加重了体内海马长时程增强（LTP）抑制，降低了 PSD95 的表达水平，增加了 APP/PS1 小鼠海马区的淀粉样β（Aβ）蛋白沉积和小胶质细胞过度激活。这些结果表明，慢性 SD 通过加速 AD 病理的发展、降低 PSD95 的表达和加重海马 LTP 抑制来加重 APP/PS1 小鼠的认知缺陷。同时，慢性 SD 通过下调 PSD95 水平和激活小胶质细胞也损害了 WT 小鼠的认知功能和突触可塑性。这些发现进一步阐明了慢性 SD 引起的 AD 认知缺陷加剧的电生理和分子机制。
