Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 211100, China.
Int J Mol Sci. 2024 Oct 29;25(21):11634. doi: 10.3390/ijms252111634.
Lack of sleep, whether acute or chronic, is quite common and negatively affects an individual's memory and cognitive function. The question of whether chronic sleep deprivation (CSD) causes cognitive impairment to arise and progress is not well studied. To investigate the effects of CSD on memory and cognition, this study began by establishing a CSD mouse model. Behavioral experiments on animals revealed that CSD induced cognitive behavioral abnormalities reminiscent of Alzheimer's disease. Western blot experiments further demonstrated a considerable increase in amyloid-β (Aβ) expression in the mouse brain following CSD. Meanwhile, the hub gene Prkcg was searched for in the cerebellum using RNA-seq and bioinformatics analysis. PKCγ (Prkcg) expression was significantly reduced, as demonstrated by RT-qPCR and Western blot validations. Additionally, CSD was associated with downregulated CREB expression, decreased expression of the endothelin-converting enzyme (ECE1), and increased phosphorylation of ERK1/2 downstream of PKCγ. These findings suggested that CSD down-regulated PKCγ expression, decreased ECE1 expression, impaired Aβ degradation, and affected the PKCγ/ERK/CREB pathway and the synthesis of memory-related proteins. Overall, this study highlighted how CSD modulated PKCγ-related metabolism, impacting Aβ clearance and the production of memory-related proteins. Such insights are crucial for understanding and preventing sporadic Alzheimer's disease (sAD) associated with CSD.
睡眠不足无论是急性还是慢性的，都很常见，会对个体的记忆和认知功能产生负面影响。慢性睡眠剥夺（CSD）是否会导致认知障碍的发生和发展，这个问题还没有得到很好的研究。为了研究 CSD 对记忆和认知的影响，本研究首先建立了 CSD 小鼠模型。对动物的行为实验表明，CSD 诱导的认知行为异常类似于阿尔茨海默病。Western blot 实验进一步表明，CSD 后小鼠大脑中的淀粉样蛋白-β（Aβ）表达显著增加。同时，使用 RNA-seq 和生物信息学分析在小脑内搜索 hub 基因 Prkcg。通过 RT-qPCR 和 Western blot 验证，发现 PKCγ（Prkcg）的表达显著降低。此外，CSD 与 CREB 表达下调、内皮素转换酶 1（ECE1）表达减少以及 PKCγ 下游的 ERK1/2 磷酸化增加有关。这些发现表明，CSD 下调了 PKCγ 的表达，降低了 ECE1 的表达，损害了 Aβ 的降解，并影响了 PKCγ/ERK/CREB 通路和记忆相关蛋白的合成。总的来说，这项研究强调了 CSD 如何调节与 PKCγ 相关的代谢，影响 Aβ 的清除和记忆相关蛋白的产生。这些见解对于理解和预防与 CSD 相关的散发性阿尔茨海默病（sAD）至关重要。
