Stud for the mechanism of aging and anesthesia-related sleep disorder and its treatment.

在本研究中，虽然在大鼠中证实了与年龄相关的睡眠障碍，但我们无法识别成年大鼠和老年大鼠之间每个睡眠阶段的长度差异。然后，我们还研究了麻醉后睡眠障碍，并确定了两种类型（GABA_A受体激活[GABA型]或NMDA受体抑制[NMDA型]）麻醉剂诱导的睡眠障碍的差异。我们发现氯胺酮（NMDA型）麻醉后几天REM睡眠显著增加，而异丙酚麻醉前后各睡眠阶段无显著差异。氯胺酮所致的麻醉后睡眠障碍与手术后睡眠障碍相似，被认为是术后呼吸和心血管并发症的主要因素。因此，氯胺酮诱导的麻醉后睡眠障碍可用作手术后睡眠障碍模型。此外，这种麻醉后睡眠障碍几乎完全被icv食欲素A或神经肽S拮抗。如果开发出在血浆中未代谢并在全身给药后穿透血脑屏障的前蛋白A或神经肽S类似物，我们可能能够治疗手术后睡眠障碍。

In this study, although age-related sleep disorder was confirmed in rats, we could not recognize a difference with the length of each sleep stage between adult and aged rats. Then, we also studied post-anesthesia sleep disorder and determine the difference of sleep disorder after both type(GABA_A receptor activation[GABA type] or NMDA receptor inhibition[NMDA-type]) of anesthetic agent-induced anesthesia. We found that REM sleep significantly increased a few days after ketamine (NMDA-type) anesthesia while no significant differences in each sleep stage between pre- and post propofol anesthesia were observed. Ketamine-induced post-anesthesia sleep disorder is similar to post-surgical sleep disorder that is considered as a main factor of postoperative respiratory and cardiovascular complications. Thus, ketamine-induced post-anesthesia sleep disorder may be used as a post-surgical sleep disorder model. In addition, this post-anesthesia sleep disorder was almost fully antagonized by icv orexin A or neuropeptide S. If prexin A or neuropeptide S analogues that are un-metabolized in the plasma and penetrated into blood brain barrier after their systemic administration will be developed, we may be able to treat post-surgical sleep disorder.