Limits...
Increased orexin expression promotes sleep/wake disturbances in the SOD1-G93A mouse model of amyotrophic lateral sclerosis.

Liu R, Sheng ZF, Cai B, Zhang YH, Fan DS - Chin. Med. J. (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Peking University Third Hospital, Beijing 100191, China.

ABSTRACT

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 in ALS. In this study, we used SOD1-G93A transgenic mice as an ALS 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.

Show MeSH

Related in: MedlinePlus

Disturbances in sleep and wakefulness in SOD1-G93A transgenic mice. EEG/EMG recordings for 24 hours from the SOD1-G93A transgenic mice and littermate control mice at 90 days and 120 days of age. (a) TST, NREM, and DS are significantly decreased in the 90-day SOD1-G93A transgenic mice. WAKE is significantly increased. (b) In the 120-day SOD1-G93A transgenic mice, WAKE is also significantly enhanced. Besides TST, NREM, and DS, REM is also significantly reduced. Data are expressed as mean ± standard error (n = 6–8/group). *P < 0.05 and †P < 0.01. TST: Total sleep time; WAKE: Wakefulness; REM: Rapid eye movement sleep; NREM: Non-rapid eye movement sleep; LS: Light sleep; DS: Deep sleep; EEG/EMG: Electroencephalogram/electromyogram.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4837845&req=5

Figure 1: Disturbances in sleep and wakefulness in SOD1-G93A transgenic mice. EEG/EMG recordings for 24 hours from the SOD1-G93A transgenic mice and littermate control mice at 90 days and 120 days of age. (a) TST, NREM, and DS are significantly decreased in the 90-day SOD1-G93A transgenic mice. WAKE is significantly increased. (b) In the 120-day SOD1-G93A transgenic mice, WAKE is also significantly enhanced. Besides TST, NREM, and DS, REM is also significantly reduced. Data are expressed as mean ± standard error (n = 6–8/group). *P < 0.05 and †P < 0.01. TST: Total sleep time; WAKE: Wakefulness; REM: Rapid eye movement sleep; NREM: Non-rapid eye movement sleep; LS: Light sleep; DS: Deep sleep; EEG/EMG: Electroencephalogram/electromyogram.

Mentions: Sleep/wake recordings were performed in both SOD1-G93A transgenic mice and their control groups. In the 90-day SOD1-G93A transgenic mice, across a 24-hour recording period, the total sleep time (TST) was significantly decreased ([443.23 ± 40.42 minutes] vs. [569.97 ± 39.04 minutes], P < 0.05) and wakefulness was increased ([996.78 ± 40.42 minutes] vs. [870.03 ± 39.04 minutes], P < 0.05), compared to the littermate controls. Non-rapid eye movement (NREM) sleep ([411.29 ± 35.41 minutes] vs. [533.48 ± 37.01 minutes], P < 0.05) and deep sleep (DS) ([47.35 ± 9.55 minutes] vs. [107.35 ± 11.36 minutes], P < 0.01) were also reduced. No significant difference was found in REM sleep and light sleep between the two groups for the 24-hour period [Figure 1a].


Increased orexin expression promotes sleep/wake disturbances in the SOD1-G93A mouse model of amyotrophic lateral sclerosis.

Liu R, Sheng ZF, Cai B, Zhang YH, Fan DS - Chin. Med. J. (2015)

Disturbances in sleep and wakefulness in SOD1-G93A transgenic mice. EEG/EMG recordings for 24 hours from the SOD1-G93A transgenic mice and littermate control mice at 90 days and 120 days of age. (a) TST, NREM, and DS are significantly decreased in the 90-day SOD1-G93A transgenic mice. WAKE is significantly increased. (b) In the 120-day SOD1-G93A transgenic mice, WAKE is also significantly enhanced. Besides TST, NREM, and DS, REM is also significantly reduced. Data are expressed as mean ± standard error (n = 6–8/group). *P < 0.05 and †P < 0.01. TST: Total sleep time; WAKE: Wakefulness; REM: Rapid eye movement sleep; NREM: Non-rapid eye movement sleep; LS: Light sleep; DS: Deep sleep; EEG/EMG: Electroencephalogram/electromyogram.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837845&req=5

Figure 1: Disturbances in sleep and wakefulness in SOD1-G93A transgenic mice. EEG/EMG recordings for 24 hours from the SOD1-G93A transgenic mice and littermate control mice at 90 days and 120 days of age. (a) TST, NREM, and DS are significantly decreased in the 90-day SOD1-G93A transgenic mice. WAKE is significantly increased. (b) In the 120-day SOD1-G93A transgenic mice, WAKE is also significantly enhanced. Besides TST, NREM, and DS, REM is also significantly reduced. Data are expressed as mean ± standard error (n = 6–8/group). *P < 0.05 and †P < 0.01. TST: Total sleep time; WAKE: Wakefulness; REM: Rapid eye movement sleep; NREM: Non-rapid eye movement sleep; LS: Light sleep; DS: Deep sleep; EEG/EMG: Electroencephalogram/electromyogram.
Mentions: Sleep/wake recordings were performed in both SOD1-G93A transgenic mice and their control groups. In the 90-day SOD1-G93A transgenic mice, across a 24-hour recording period, the total sleep time (TST) was significantly decreased ([443.23 ± 40.42 minutes] vs. [569.97 ± 39.04 minutes], P < 0.05) and wakefulness was increased ([996.78 ± 40.42 minutes] vs. [870.03 ± 39.04 minutes], P < 0.05), compared to the littermate controls. Non-rapid eye movement (NREM) sleep ([411.29 ± 35.41 minutes] vs. [533.48 ± 37.01 minutes], P < 0.05) and deep sleep (DS) ([47.35 ± 9.55 minutes] vs. [107.35 ± 11.36 minutes], P < 0.01) were also reduced. No significant difference was found in REM sleep and light sleep between the two groups for the 24-hour period [Figure 1a].

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Peking University Third Hospital, Beijing 100191, China.

ABSTRACT

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 in ALS. In this study, we used SOD1-G93A transgenic mice as an ALS 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.

Show MeSH
Related in: MedlinePlus