The neuroprotective effect of osthole against chronic sleep deprivation (CSD)-induced memory impairment in rats

Sleep deprivation (SD) is a frequent health problem in modern society. Osthole (Ost), a natural coumarin, has antioxidant and neuroprotective properties. This study examined the functions of Ost in chronic sleep deprivation (CSD)-induced memory deficits in rats. The CSD rat model was constructed by applying Sleep Interruption Apparatus (SIA). The protective effect of Ost on memory ability of CSD rats was evaluated through behavioral tests. Modafinil (MOD) was a positive control for investigating the mechanisms underlying the actions of Ost. The oxidative stress changes in the cortex and hippocampus of the rats, histological changes in CA1 region in the hippocampus and the protein expressions of neural plasticity markers were measured. The hippocampal neurons were isolated from rats for evaluating the neuroprotective effects of Ost on glutamate-induced neuron injury in vitro. Ost administration significantly enhanced the cognitive performance of CSD rats in the open field test, object location recognition experiment, novel object recognition experiment, and Morris water maze test. Ost could effectively normalize the levels/activities of the antioxidant enzyme system in the cortex and hippocampus. Moreover, Ost administration reversed CSD-induced abnormal state of CA1 neurocytes and the down-regulated expressions of plasticity-related genes in vivo and in vitro. Additionally, Ost also notably up-regulated the expressions of Nrf2 and HO-1 previously down-regulated in CA1 neurocytes of CSD rats and in vitro. Our findings showed that Ost alleviated CSD-induced cognitive deficits, and the activation of the Nrf2/HO-1 pathway might be involved in the neuroprotective action of Ost.