Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (6): 1094-1101.doi: 10.4103/1673-5374.270415

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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).

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