中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (6): 1094-1101.doi: 10.4103/1673-5374.270415

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

光声治疗可减轻睡眠-觉醒节律紊乱模型小鼠的认知功能障碍

  

  • 出版日期:2020-06-15 发布日期:2020-07-02
  • 基金资助:
    国家自然科学基金资助（81730033，81701371，81801380）；江苏省自然科学基金（BK20170654，BK20170129）；以及江苏省“十三五”重点人才强身健体计划（ZDRA2016069）

Photoacoustic treatment mitigates cognitive dysfunction in a model of sleep-wake rhythm disturbance

Fang Xing1 , Xin Fang1 , Xiang-Dan Gong1 , Xin Zhao1 , Ying Du1 , Zheng-Liang Ma1 , Xiao-Ping Gu1, Tian-Jiao Xia1, 2   

  1. 1 Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical Department of Nanjing University, Nanjing, Jiangsu Province, China
    2 Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu Province, China
  • Online:2020-06-15 Published:2020-07-02
  • Contact: Zheng-Liang Ma, PhD,mazhengliang1964@nju.edu.cn; Xiao-Ping Gu, PhD,xiaopinggu@nju.edu.cn; Tian-Jiao Xia, PhD, tjxia@nju.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81730033 (to XPG), No. 81701371 (to TJX), No. 81801380 (to XZ); the Natural Science Foundation of Jiangsu Province of China, No. BK20170654 (to TJX), No. BK20170129 (to XZ); and the Key Talent’s 13 th Five-Year Plan for Strengthening Health of Jiangsu Province of China, No. ZDRCA2016069 (to XPG).

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摘要：

睡眠-觉醒节律紊乱特点在于入睡时间或睡眠持续时间异常，与认知功能障碍相关。光和声刺激的光声疗法在异常的睡眠-觉醒实验中被证实是能改变睡眠模式和改善认知行为。实验目的是检测光和声干预是否能改善睡眠节律紊乱模型的睡眠觉醒节律紊乱和记忆缺陷。通过睡眠剥夺法建立睡眠-觉醒节律紊乱C57BL/6J小鼠模型，造模方法为手轻敲笼子、颠簸笼子、制造轻微噪声5 h以干扰小鼠居住环境。在实验过程中，我们利用Minimitter检测小鼠每日粗大运动，以了解睡眠觉醒节律变化，利用条件恐惧实验以了解小鼠认知情况。结果显示，40 Hz闪烁频率的蓝光在小鼠相对觉醒期干预1 h显著改善了由睡眠剥夺导致的24 h相位偏移和记忆缺陷。但是，40 Hz蓝光在睡眠觉醒交界期和相对睡眠期的干预以及2 Hz蓝光在这3个时间点(相对觉醒期、相对睡眠期、睡眠觉醒交界期)的干预没有改善昼夜节律偏移和记忆缺陷。此外，相对觉醒期2000 Hz声音干预也能改善24 h相位偏移和记忆减退，但是440 Hz和4000 Hz声干预没有改善模型小鼠节律。综上，这些结果揭示了光声疗法能有效纠正异常的睡眠-觉醒模式，改善睡眠剥夺造成的睡眠-觉醒节律紊乱中的认知障碍。

orcid: 0000-0001-6524-4186 (Zheng-Liang Ma) 

         0000-0002-8218-7299 (Xiao-Ping Gu) 

         0000-0002-7616-4651 (Tian-Jiao Xia)

关键词: 睡眠剥夺, 昼夜节律, 睡眠-觉醒节律, 节律紊乱, 节律偏移, 认知损害, 条件恐惧, 光干预, 声干预, 光声治疗

Abstract: Sleep-wake rhythm disturbances, which are characterized by abnormal sleep timing or duration, are associated with cognitive dysfunction. Photoacoustic treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improv- ing cognitive behavior in abnormal sleep-wake pattern experiments. In this study, we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance model. We established a model of sleep rhythm disturbance in C57BL/6J mice via a sleep deprivation method involving manual cage tapping, cage jostling, and nest disturbance. We used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive func- tion. Our results indicated that an intervention in which the mice were exposed to blue light (40-Hz flickering frequency) for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep deprivation. However, interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points, as well as 2 Hz-blue light at 3 intervention time points (subjective day time, subjective night time, and offset time points), had no positive effects on circadian rhythm shift or memory deficits. Additionally, a 2000-Hz sound intervention during subjective day time attenuated the 24-hour-acrophase shift and memory decline, while 440-Hz and 4000-Hz sounds had no effect on circadian rhythms. Overall, these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake rhythm. All animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University, China (approval No. 20171102) on November 20, 2017.

Key words: circadian rhythm, cognitive impairment, fear conditioning, light intervention, photoacoustic treatment, rhythm disturbance, rhythm shift, sleep deprivation, sleep-wake rhythm, sound intervention