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Differential effects of AKT1 and AKT2 on sleep–wake activity under basal conditions and in response to LPS challenge in mice

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Abstract

Infectious challenge can trigger alterations in sleep–wake behavior. Accumulating evidence has shown that the serine/threonine kinases Akt1 and Akt2 are important targets in both physiological and infectious signaling processes. However, the involvement of Akt1 and Akt2 in sleep–wake activity under basal conditions and in response to inflammatory stimulation has not been established. In the present study, we assessed the precise role of Akt1 and Akt2 in sleep–wake behavior using electroencephalography (EEG)/electromyography (EMG) data from Akt1- and Akt2-deficient mice and wild-type (WT) mice. The results showed that both Akt1 and Akt2 deficiency affect sleep–wake activity, as indicated by reduced nonrapid eye movement (NREM) sleep and increased wakefulness in mutant mice compared to WT mice. Sleep amount and intensity (delta, theta and alpha activity) at night were also drastically attenuated in Akt1- and Akt2-deficient mice. Moreover, since Akt1 and Akt2 are involved in immune responses, we assessed their roles in the sleep response to the inflammatory stimulus lipopolysaccharide (LPS) throughout the following 24 h. We observed that the decrease in wakefulness and increase in NREM sleep induced by LPS were restored in Akt1 knockout mice but not in Akt2 knockout mice. Correspondingly, the decrease in the number of positive orexin-A neurons induced by LPS was abrogated in Akt1 knockout mice but not in Akt2 knockout mice. Our results revealed that both Akt1 and Akt2 deficiency affect the sleep response under basal conditions, but only Akt1 deficiency protects against the aberrant changes in sleep behavior induced by peripheral immune challenge.

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Acknowledgements

This study was supported by Wuxi Municipal Bureau on Science and Technology (Y20222012).

Funding

This study was supported by Wuxi Municipal Bureau on Science and Technology (Y20222012).

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Authors and Affiliations

  1. Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Wuxi, 214000, Jiangsu Province, People’s Republic of China

    Peng Zhao

  2. Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, People’s Republic of China

    Meng Cui, Pengfei Meng, Shaohe Wang, Qingyuan Feng, Guangming Liu & Peng Zhao

Authors
  1. Meng Cui
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  2. Pengfei Meng
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  3. Shaohe Wang
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  4. Qingyuan Feng
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  5. Guangming Liu
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  6. Peng Zhao
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Contributions

Peng Zhao designed the experiments; Meng Cui, Pengfei Meng, Qingyuan Feng, and Guangming Liu performed the experiments and analyzed the data; Meng Cui prepared the manuscript.

Corresponding author

Correspondence to Peng Zhao.

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All authors declare that they have no conflict of interest.

Ethical committee permission

Experimental protocols were approved by the Animal Ethics Committee of Jiangnan University (JN. No20190415c0420228[83]).

Animals

Male C57BL/6 mice were obtained from Shanghai SLAC Laboratory Animal Co., Ltd. Shanghai Jiaotong University graciously donated Akt1 knockout mice and Akt2 knockout mice.

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Cui, M., Meng, P., Wang, S. et al. Differential effects of AKT1 and AKT2 on sleep–wake activity under basal conditions and in response to LPS challenge in mice. Sleep Biol. Rhythms (2024). https://doi.org/10.1007/s41105-024-00519-y

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