Abstract

Sleep disorder has become a prevalent issue in current society and is connected with the deterioration of neurobehaviors such as mood, cognition and memory. Ellagic acid (EA) is a phenolic phytoconstituent extracted from grains and fruits that has potent neuroprotective properties. This research aimed to study the alleviative effect and mechanism of EA on memory impairment and anxiety caused by sleep deprivation (SD). EA ameliorated behavioral abnormalities in SD mice, associated with increased dendritic spine density, and reduced shrinkage and loss of hippocampal neurons. EA reduced the inflammatory response and oxidative stress injury caused by SD, which may be related to activation of the Nrf2/HO-1 pathway and mitigation of the TLR4-induced inflammatory response. In addition, EA significantly reduced the mortality and ROS levels in glutamate (Glu)-induced hippocampal neuron injury, and these effects of EA were enhanced in TLR4 siRNA-transfected neurons. However, knockdown of Nrf2 dramatically restrained the protective impact of EA on Glu-induced toxicity. Taken together, EA alleviated memory impairment and anxiety in sleep-deprived mice potentially by inhibiting TLR4 and activating Nrf2. Our findings suggested that EA may be a promising nutraceutical ingredient to prevent cognitive impairment and anxiety caused by sleep loss.

Highlights

  • Sleep is a fundamental conserved physiological process of the human body, and the quality and quantity of sleep can affect individual health status and quality of life [1]

  • We found that the potential molecular mechanism for the effects of Ellagic acid (EA) versus sleep deprivation (SD) was related to the modulation of TLR4 and Nuclear factor erythroid 2-related factor 2 (Nrf2)

  • Consistent with the behavioral data in our study and others, EA had a normalizing effect on www.aging-us.com the levels of proinflammatory cytokines and oxidative stress parameters in the hippocampus of SD mice

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Summary

Introduction

Sleep is a fundamental conserved physiological process of the human body, and the quality and quantity of sleep can affect individual health status and quality of life [1]. It has been well documented that inadequate sleep is detrimental to human health [4, 5]. Sleep deprivation has long been known to impair neurobehavior. This cognitive function impairment is related to increased oxidative stress and inflammation in the brain. Glu generates oxidative stress by various mechanisms, which leads to increased reactive oxygen species (ROS) production. The abnormal production of ROS causes oxidation of biological macromolecules and the expression of inflammatory mediators and genes, leading to an increase in the risk of neurodegenerative diseases

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