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|Increased Orexin Expression Promotes Sleep/Wake Disturbances in the SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis|
|Liu, Rong1; Sheng, Zhao-Fu2; Cai, Bing1; Zhang, Yong-He2; Fan, Dong-Sheng1|
|关键词||Amyotrophic Lateral Sclerosis Orexin Sleep/Wake Disturbance|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
Background: Sleep/wake disturbances in patients with amyotrophic lateral sclerosis (ALS) are well-documented, however, no animal or mechanistic studies on these disturbances exist. Orexin is a crucial neurotransmitter in promoting wakefulness in sleep/wake regulation, and may play an important role in sleep disturbances inALS. In this study, we used SOD1-G93Atransgenic mice as anALS mouse model to investigate the sleep/wake disturbances and their possible mechanisms in ALS.
Methods: Electroencephalogram/electromyogram recordings were performed in SOD1-G93A transgenic mice and their littermate control mice at the ages of 90 and 120 days, and the samples obtained from these groups were subjected to quantitative reverse transcriptase-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay.
Results: For the first time in SOD1-G93A transgenic mice, we observed significantly increased wakefulness, reduced sleep time, and up-regulated orexins (prepro-orexin, orexin A and B) at both 90 and 120 days. Correlation analysis confirmed moderate to high correlations between sleep/wake time (total sleep time, wakefulness time, rapid eye movement [REM] sleep time, non-REM sleep time, and deep sleep time) and increase in orexins (prepro-orexin, orexin A and B).
Conclusion: Sleep/wake disturbances occur before disease onset in this ALS mouse model. Increased orexins may promote wakefulness and result in these disturbances before and after disease onset, thus making them potential therapeutic targets for amelioration of sleep disturbances in ALS. Further studies are required to elucidate the underlying mechanisms in the future.
|资助机构||National Natural Science Foundation of China|
|作者单位||1.Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China|
2.Peking Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing 100191, Peoples R China
|Liu, Rong,Sheng, Zhao-Fu,Cai, Bing,et al. Increased Orexin Expression Promotes Sleep/Wake Disturbances in the SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis[J]. CHINESE MEDICAL JOURNAL,2015,128(2):239-244.|
|APA||Liu, Rong,Sheng, Zhao-Fu,Cai, Bing,Zhang, Yong-He,&Fan, Dong-Sheng.(2015).Increased Orexin Expression Promotes Sleep/Wake Disturbances in the SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis.CHINESE MEDICAL JOURNAL,128(2),239-244.|
|MLA||Liu, Rong,et al."Increased Orexin Expression Promotes Sleep/Wake Disturbances in the SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis".CHINESE MEDICAL JOURNAL 128.2(2015):239-244.|
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