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19 April 2019 : Animal Research  

Effects of Sleep Deprivation (SD) on Rats via ERK1/2 Signaling Pathway

Li Wang12ABE, Youyi Gu2ABE, Jingjing Zhang2CDF, Li Gong3EF*

DOI: 10.12659/MSM.913839

Med Sci Monit 2019; 25:2886-2895


BACKGROUND: Sleep deprivation (SD) is common in humans, and sleep loss has a significant influence on health and produces related diseases. Orexin-A has been demonstrated to play a role in physiological processes, including feeding, sleep/wake cycle, and energy metabolism. The aim of this study was to investigate the effect of SD on rats and to define the underlying mechanism.

MATERIAL AND METHODS: We constructed an SD rat model. The Morris water maze test was used to assess rat learning and memory. Imaging of hippocampus and hippocampal tissue in rats were captured by magnetic resonance imaging or electron microscopy. We used the CCK-8 kit to assess cell viability. The level of protein was measured using Western blot analysis, and qRT-PCR was used to evaluate mRNA level.

RESULTS: SD rats had poorer learning and memory and had damage to the hippocampus. SD resulted in shrinkage of hippocampal volume and encephalocele size. SD increased the expression of Orexin-A, OX1R, OX2R, and PARP-1, and decreased the expression of ERK1/2 and p-ERK1/2. Orexin-A (0–10 μM) improved neuron viability, whereas orexin-A (10–100 μM) attenuated neuron viability. SB334867 treatment reduced the viability of neurons treated with orexin-A. NU1025 treatment increased cell viability, especially in neurons treated with orexin-A. SB334867 treatment decreased the p-ERK1/2 levels in neurons treated with orexin-A. NU1025 increased the expression of p-ERK1/2 in neurons treated with orexin-A.

CONCLUSIONS: SD decreases learning and memory through damage to the hippocampus. Higher concentrations of orexin-A had a major negative effect on hippocampal neurons via OX1R and PARP-1 through inhibition of the ERK1/2 signaling pathway.

Keywords: Hippocampus, orexins, Sleep Deprivation, Intracellular Signaling Peptides and Proteins, Memory, Mitogen-Activated Protein Kinase 3, Neurons, Neuropeptides

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Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville,

DOI: 10.12659/MSM.942960

Med Sci Monit 2023; 29:e942960


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750