Soy isoflavones protects against cognitive deficits induced by chronic sleep deprivation via alleviating oxidative stress and suppressing neuroinflammation

Abstract

Mounting evidence suggests that there is a close association between chronic sleep deprivation (CSD) and cognitive deficits. The animal model of CSD‐induced cognitive deficits is commonly used to seek potential treatments. Soy isoflavones (SI) have been reported to possess antioxidant, anti‐inflammation, and neuroprotective effects. In the present study, the effects of SI on CSD‐induced memory impairment were investigated. The mice were subjected to the sleep interruption apparatus and continuously sleep deprived for 2 weeks, while orally administrated with SI (10, 20, and 40 mg/kg) or Modafinil (MOD,100 mg/kg) during the CSD process. Immediately after the SD protocol, cognitive performance of mice was evaluated by the object location recognition (OLR) test, the novel object recognition (NOR) test, and the Morris water maze (MWM) task, as well as the hippocampus, was extracted for evaluation of oxidative stress parameters and inflammation levels through biochemical parameter assay and western blotting analysis. The results showed that SI administration remarkably improved the cognitive performance of CSD‐treated mice in OLR, NOR, and MWM tests. In addition, SI significantly elevated total antioxidant capacity and superoxide dismutase enzyme activities, decreased malondialdehyde level, promoting antioxidant element nuclear erythroid‐2‐related factor 2, and its downstream targets, including heme oxygenase 1, and quinone oxidoreductase 1 protein expressions. Moreover, SI treatment significantly suppressed nuclear factor kappa B p65, nitric oxide synthase, and cyclooxygenase 2 activation, as well as the pro‐inflammatory cytokines (Tumor necrosis factor‐α [TNF‐α], interleukin‐6 [IL‐6], and interleukin‐1β [IL‐1β]) release in the hippocampus of CSD‐treated mice. In summary, the current study provides an insight into the potential of SI in treatment of cognitive deficits by CSD.

Mitochondrial antioxidant elamipretide improves learning and memory impairment induced by chronic sleep deprivation in mice

“…The levels of pro‐inflammatory cytokines were found to be increased in the peripheral blood of patients with sleep disorders (Irwin et al., 2016 ; Xia et al., 2021 ). In addition, sleep deprivation significantly elevated the levels of proinflammatory cytokines including IL‐1β, IL‐6, and TNF‐α in the hippocampus and resulted in cognitive impairment during the novel object recognition test (Lu et al., 2022 ). In line with these previous studies, the results showed that the levels of IL‐1β, IL‐6, and TNF‐α were increased in the hippocampus of the mice exposed to CSD, which contributed to the observed cognitive decline.…”

The Devastating Effects of Sleep Deprivation on Memory: Lessons from Rodent Models

“…Chronic SD promotes the transformation of microglia into the neurotoxic M1 phenotype and subsequently induces the NF-κB pathway to increase the release of pro-inflammatory factors (TNF-α, IL-6), causing neuroinflammatory response, aggravating hippocampal neuron damage, and affecting cognitive function [ 55 ]. Further studies found that SD increased the protein levels of the pro-inflammatory cytokines TNF-α, IL1-β, IL-6, and IL-8 but decreased the protein levels of the anti-inflammatory cytokines IL-4 and IL-10 in the rat hippocampus [ 55 , 57 , 102 , 103 , 104 ]. Serum levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) increased in SD rats after 24 h of SD, and the effect was more significant in cerebrospinal fluid after 72 h of SD (IL-1β: 30.2 ± 12.8 pg·mL −1 →43.6.8 ± 9.4 pg·mL −1 ; IL-6: 28.8 ± 9.3 pg·mL −1 →37.8 ± 7.4 pg·mL −1 ; TNF-α:19.1 ± 6.3 pg·mL −1 →21.8 ± 7.4 pg·mL −1 ).…”

Soy isoflavones alleviate lipopolysaccharide-induced depressive-like behavior by suppressing neuroinflammation, mediating tryptophan metabolism and promoting synaptic plasticity

“…9 A recent study showed that SI offer good therapeutic and/or preventive potential for Parkinson's disease (PD), which is associated with dysregulated mitophagy. 10 Our previous studies had found that SI can protect against cognitive deficits induced by chronic sleep deprivation by alleviating oxidative stress and suppressing neuroinflammation, 11 as well as reverse chronic ethanol exposure-induced cognitive dysfunction by enhancing synaptic plasticity and inhibiting neuronapoptosis. 12 Depression evokes the activation of microglia and promotes the production of proinflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cortex and hippocampus of mice.…”