Abstract
Sleep deprivation is commonplace in modern society, Short periods of continuous sleep deprivation (SD) may negatively affect brain and behavioral function and may lead to vehicle accidents and medical errors. Tanshinone IIA (Tan IIA) is an important lipid-soluble component of Salvia miltiorrhiza, which could exert neuroprotective effects. The aim of this study was to investigate the mechanism of neuroprotective effect of Tan IIA on acute sleep deprivation-induced cognitive dysfunction in rats. Tan IIA ameliorated behavioral abnormalities in sleep deprived rats, enhanced behavioral performance in WMW and NOR experiments, increased hippocampal dendritic spine density, and attenuated atrophic loss of hippocampal neurons. Tan IIA enhanced the expression of CB1, PI3K, AKT, STAT3 in rat hippocampus and down-regulated the expression ratio of Bax to Bcl-2. These effects were inhibited by cannabinoid receptor 1 antagonist (AM251). In conclusion, Tan IIA can play a neuroprotective role by activating the CNR1/PI3K/AKT signaling pathway to antagonize apoptosis in the hippocampus and improve sleep deprivation-induced spatial recognition and learning memory dysfunction in rats. Our study suggests that Tan IIA may be a candidate for the prevention of sleep deprivation-induced dysfunction in spatial recognition and learning memory.
Highlights
Long enough undisturbed sleep is a pillar of human health, but sleep deprivation is commonplace in modern society, and chronic sleep deprivation can damage human health, increasing the risk of cardiovascular disease, obesity (Leslie, 2012; Wang et al, 2019), and is associated with reduced cognitive function (Killgore, 2010; Javaheripour et al, 2019; Ma et al, 2020)
We used bioinformatics-related methods to find that the key target of Tanshinone IIA (Tan IIA) for the treatment of patients with cognitive dysfunction syndrome may be CNR1
Our study showed that Tan IIA has a neuroprotective effect on acute sleep deprivation-induced cognitive impairment in rats, and its mechanism of action may be activating the CNR1/phosphatidylinositol 3-kinase (PI3K)/ AKT pathway in the hippocampal region, ameliorating hippocampal neuronal cell injury and inhibiting hippocampal cell apoptosis
Summary
Long enough undisturbed sleep is a pillar of human health, but sleep deprivation is commonplace in modern society, and chronic sleep deprivation can damage human health, increasing the risk of cardiovascular disease, obesity (Leslie, 2012; Wang et al, 2019), and is associated with reduced cognitive function (Killgore, 2010; Javaheripour et al, 2019; Ma et al, 2020). A previous study found that Tan IIA improved the performance of streptozotocin-induced APP/PS1 transgenic mice in NOR tests demonstrating beneficial effects on cognitive memory function (He et al, 2020). Another study found that Tan IIA alleviated cognitive dysfunction caused by other factors, such as diabetesrelated, chemokine CC motif ligand 2 (CCL2)-induced, vascular dementia in rats, in experiments that relied on MWM assessment (Chen et al, 2018; Liao et al, 2020; Kong et al, 2021). The effect of Tan IIA on behavioral function in sleep deprivation model animals has not been elucidated, and whether Tan IIA has an effect on sleep deprivation-induced cognitive dysfunction has not been reported
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