| Summary: | Background: Many neurobehavioral processes, including psychomotor, cognitive, and affection are negatively impacted by sleep deprivation (SD), which may be harmful to a person's physical and mental health. Heat shock proteins (Hsps) have been demonstrated to play a protective role in a number of neurodegenerative diseases and are essential for maintaining intracellular protein homeostasis, but their roles in SD remain elusive. Methods: A mouse SD model was constructed using a modified multi-platform water environment method. The cognitive function was tested by novel object recognition test and Y-maze test, and anxiety-like behaviors were assessed by open field test (OFT). Protein expression was determined by Western blotting assay and ELISA assay. Results: We found that SD could profoundly enhance anxiety levels and impair cognitive function in mice. SD also reduced the expression levels of p-cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) and increased microglial activation and neuroinflammatory response in the hippocampus of mice. The intranasal injection of human recombinant Hsp70 protein could alleviate SD-induced anxiety and cognitive impairment, as well as restore pCREB and BDNF levels and reduce microglia-induced neuroinflammation in the hippocampus of SD mice. Conclusions: Hsp70 treatment might serve as a potential treatment for mitigating SD-related unfavorable symptoms.
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