The administration of rhBmal1 reduces sleep deprivation-induced anxiety and cognitive impairment in mice

Abstract

Background: In mammals, circadian rhythms control metabolism, immunological response and reproductive processes. Bmal1 (brain and muscle Arnt-like protein-1) is a key element in the regulation of circadian rhythms.

Methods: This investigation explores the pathophysiological effects of sleep deprivation in a mouse model as well as the potential underlying mechanisms. A mouse sleep deprivation model was constructed using a modified multi-platform water environment method. The anxiety-like behaviours of mice were assessed by the open field test and elevated plus maze, and the cognitive function of mice was tested by the nest-building test. The expression levels of targeted genes were determined by Western blotting assay and RT-qPCR assay.

Results: We found that sleep deprivation profoundly enhanced anxiety levels and impaired cognitive function in mice. Sleep deprivation also reduced the expression levels of Bmal1 and BDNF (brain-derived neurotrophic factor) and increased oxidative stress in the hippocampus of mice. The intraperitoneal injection of human recombinant rhBmal1 protein alleviated sleep deprivation-induced anxiety and cognitive impairment, restored Bmal1 and BDNF levels, and reduced oxidative stress in the hippocampus of mice.

Conclusions: rhBmal1 treatment might serve as a potential therapy for mitigating sleep deprivation-related unfavourable symptoms.

Keywords: Bmall; cognitive function; mice; sleep deprivation.