Department of Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Neuroscience. 2010 May 19;167(3):573-82. doi: 10.1016/j.neuroscience.2010.01.059. Epub 2010 Feb 4.
Senescence-accelerated mouse prone/8 (SAMP8) mice are known to exhibit age-related deterioration in sleep-wake architecture compared with senescence-accelerated mouse resistant/1 (SAMR1) mice. We investigated whether treatment with Am80 (Tamibarotene), a retinoic acid receptor agonist, would improve sleep in 9-10-month-old SAMP8 mice. One week of Am80 administration improved the decrease in rapid eye movement (REM) sleep shown by SAMP8 mice. Real-time RT-PCR analysis demonstrated an impairment in the hippocampal retinoid cascade (retinoic acid receptor alpha and transthyretin) in SAMP8 in comparison to SAMR1 mice. Am80 treatment induced an increase in mRNA expression in the vesicular acetylcholine transporter in the brainstem and transthyretin in the hippocampus. Furthermore, decreased cortical acetylcholine content in SAMP8 was improved by Am80 administration. Decreased non-REM sleep and delta oscillation were also observed in SAMP8 mice; however, this was not improved by Am80 administration. These results partially support the hypothesis that the effects of aging on sleep-wake architecture are improved by the activation of retinoic acid receptors. The improvement may be induced by the activation of the cholinergic pathway.
快速眼动（REM）睡眠减少，是加速老化 8 号小鼠（SAMP8）与抗老化加速 1 号小鼠（SAMR1）相比，在睡眠-觉醒结构上出现与年龄相关的恶化的表现之一。我们研究了视黄酸受体激动剂 Am80（Tamibarotene）治疗是否可以改善 9-10 个月大的 SAMP8 小鼠的睡眠。一周的 Am80 给药改善了 SAMP8 小鼠的 REM 睡眠减少。实时 RT-PCR 分析表明，与 SAMR1 小鼠相比，SAMP8 小鼠的海马视黄酸级联（视黄酸受体α和转甲状腺素）受损。Am80 治疗诱导脑桥中的囊泡乙酰胆碱转运体和海马中的转甲状腺素的 mRNA 表达增加。此外，SAMP8 中的皮质乙酰胆碱含量降低，通过 Am80 给药得到改善。在 SAMP8 小鼠中还观察到非快速眼动（NREM）睡眠和 delta 振荡减少；然而，Am80 给药并不能改善这一点。这些结果部分支持这样的假设，即视黄酸受体的激活改善了睡眠-觉醒结构随年龄的变化。这种改善可能是通过胆碱能途径的激活引起的。
