Sleep disruptions promote increases of amyloid β (Aβ) and tau in the brain and increase Alzheimer’s disease (AD) risk, but the precise mechanisms that give rise to sleep disturbances have yet to be defined. The thalamic reticular nucleus (TRN) is essential for sleep maintenance and for the regulation of slow-wave sleep (SWS). We examined the TRN in transgenic mice that express mutant human amyloid precursor protein (APP) and found reduced neuronal activity, increased sleep fragmentation, and decreased SWS time as compared to nontransgenic littermates. Selective activation of the TRN using excitatory DREADDs restored sleep maintenance, increased time in SWS, and reduced amyloid plaque load in both hippocampus and cortex. Our findings suggest that the TRN may play a major role in symptoms associated with AD. Enhancing TRN activity might be a promising therapeutic strategy for AD.

中文翻译：

---

恢复丘脑网状核的活动可改善小鼠的睡眠结构并减少 Aβ 积累


睡眠中断会促进大脑中 β 淀粉样蛋白 (Aβ) 和 tau 蛋白的增加，并增加阿尔茨海默病 (AD) 的风险，但引起睡眠障碍的确切机制尚未确定。丘脑网状核 (TRN) 对于睡眠维持和慢波睡眠 (SWS) 的调节至关重要。我们检查了表达突变型人类淀粉样前体蛋白 (APP) 的转基因小鼠的 TRN，发现与非转基因同窝小鼠相比，神经元活动减少，睡眠碎片化增加，SWS 时间缩短。使用兴奋性 DREADD 选择性激活 TRN 可恢复睡眠维持，增加 SWS 时间，并减少海马和皮质中的淀粉样斑块负荷。我们的研究结果表明 TRN 可能在 AD 相关症状中发挥重要作用。增强 TRN 活性可能是治疗 AD 的一种有前景的策略。