Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (4): 17-23.doi: 10.6040/j.issn.1671-7554.0.2021.0264

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Study on the mechanism of Suvorexant treatment ameliorates learning and memory impairment in chronic sleep deprivation mice model

SHAO Na1, YIN Hao2, LI Yaran2, ZHANG Baokun1, HUANG Weiwei2, LU Shanshan2, TANG Jiyou1,2   

  1. 1. Department of Neurology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250014, Shandong, China;
    2. Department of Neurology, The First Affiliated Hospital of Shandong First Medical University &
    Shandong Provincial Qianfoshan Hospital, Shandong Institute of Neuroimmunology, Shandong Key Laboratory of Rheumatic Disease and Translation Medicine. Jinan 250014, Shandong, China
  • Online:2022-04-10 Published:2022-04-22

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Abstract: Objective To observe the effects of Orexin dual receptor antagonist(Suvorexant)on learning and memory in chronic sleep deprivation(SD)mice, and to explore the role of astrocytes in Orexin system affecting learning and memory in SD mice model. Methods Wild-type mice aged 8-10 weeks were randomly divided into 4 groups: control group, saline control group, chronic SD group and Suvorexant intervention group. The mice were subjected to sleep disturbance for 4 weeks by simulating artificial stroking with a sleep deprivation chamber with 20 hours per day. And during SD, the Suvorexant intervention group was given an intraperitoneal injection of Suvorexant at the same time(30 mg/kg, 4 weeks); the spatial learning and memory of mice were evaluated with Morris water maze, and the expression of Orexin-A in the lateral hypothalamus and the expression of astrocyte marker glialfibrillary acidic protein(GFAP)in the hippocampus were observed with immunohistochemistry and Western blotting. Results The expression of Orexin-A was significantly increased in the lateral hypothalamus after 4 weeks of SD, and there was no difference in body weight among the groups during the intervention. Suvorexant treatment significantly improved learning and memory after chronic SD. Compared with the SD group, the Suvorexant intervention group had decreased escape latency and an increased number of platform crossings(P<0.05). The expression of GFAP protein increased in the hippocampus of SD mice, and the morphological manifestations showed that the cells were reactive: the cell body was enlarged, the synapse became longer, and the expression in the positive area was significantly increased. Compared with the SD group, the Suvorexant intervention group had decreased expression of GFAP(P<0.05). Conclusion Suvorexant treatment improves spatial learning and memory in chronic SD mice and reduces the expression of reactive astrocytes in the hippocampus, and the activation of astrocytes may be involved in this process.

Key words: Orexin dual receptor antagonist, Chronic sleep deprivation, Learning and memory, Astrocytes, Hippocampus

CLC Number: 

  • R741
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