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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.

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mRNA levels of orexin receptors. Q-PCR of orexin-1 receptor mRNA show no significant difference in the hypothalamus (a) and brain stem (b) of the 90 and 120 days SOD1-G93A transgenic mice than controls. No significant difference is found in orexin-2 receptor mRNA in the hypothalamus (c) and brain stem (d) of the 90 and 120 days SOD1-G93A transgenic mice than controls. HT: Hypothalamus; BS: Brain stem; PCR: Polymerase chain reaction.
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Figure 4: mRNA levels of orexin receptors. Q-PCR of orexin-1 receptor mRNA show no significant difference in the hypothalamus (a) and brain stem (b) of the 90 and 120 days SOD1-G93A transgenic mice than controls. No significant difference is found in orexin-2 receptor mRNA in the hypothalamus (c) and brain stem (d) of the 90 and 120 days SOD1-G93A transgenic mice than controls. HT: Hypothalamus; BS: Brain stem; PCR: Polymerase chain reaction.

Mentions: Q-PCR analysis revealed no significant difference in the mRNA levels of OX1R [Figure 4a and 4b] and OX2R [Figure 4c and 4d] in the hypothalamus or the brain stem between the SOD1-G93A transgenic mice and controls.


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)

mRNA levels of orexin receptors. Q-PCR of orexin-1 receptor mRNA show no significant difference in the hypothalamus (a) and brain stem (b) of the 90 and 120 days SOD1-G93A transgenic mice than controls. No significant difference is found in orexin-2 receptor mRNA in the hypothalamus (c) and brain stem (d) of the 90 and 120 days SOD1-G93A transgenic mice than controls. HT: Hypothalamus; BS: Brain stem; PCR: Polymerase chain reaction.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: mRNA levels of orexin receptors. Q-PCR of orexin-1 receptor mRNA show no significant difference in the hypothalamus (a) and brain stem (b) of the 90 and 120 days SOD1-G93A transgenic mice than controls. No significant difference is found in orexin-2 receptor mRNA in the hypothalamus (c) and brain stem (d) of the 90 and 120 days SOD1-G93A transgenic mice than controls. HT: Hypothalamus; BS: Brain stem; PCR: Polymerase chain reaction.
Mentions: Q-PCR analysis revealed no significant difference in the mRNA levels of OX1R [Figure 4a and 4b] and OX2R [Figure 4c and 4d] in the hypothalamus or the brain stem between the SOD1-G93A transgenic mice and controls.

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