Hanqing Tang1, Keming Li2, Xibin Dou2, Yufeng Zhao2, Chunchuan Huang2, Fangyi Shu2. 1. School of Basic Medicine, Youjiang Medical University for Nationalities, No. 98, Chengxiang Road, Youjiang District, Baise City, Guangxi Province 533000, China. Electronic address: tanghq_hanqing@163.com. 2. School of Basic Medicine, Youjiang Medical University for Nationalities, No. 98, Chengxiang Road, Youjiang District, Baise City, Guangxi Province 533000, China.
Abstract
AIM: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIM: 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. MAIN METHODS: 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. KEY FINDINGS: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. SIGNIFICANCE: 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.
Authors: István Gyertyán; Jana Lubec; Alíz Judit Ernyey; Christopher Gerner; Ferenc Kassai; Predrag Kalaba; Kata Kozma; Iva Cobankovic; Gábor Brenner; Judith Wackerlig; Eva Franschitz; Ernst Urban; Thierry Langer; Jovana Malikovic; Gert Lubec Journal: Sci Rep Date: 2021-12-14 Impact factor: 4.379