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藏红花通过上调沉默信息调节因子-1 和脑源性神经营养因子缓解大鼠的精神分裂样症状。

Crocin alleviates schizophrenia-like symptoms in rats by upregulating silent information regulator-1 and brain derived neurotrophic factor.

机构信息

Open Mental Department of Qingdao Mental Health Center, Qingdao University, No. 299 Nanjing Road, Qingdao 266034, Shandong, China.

Open Mental Department of Qingdao Mental Health Center, Qingdao University, No. 299 Nanjing Road, Qingdao 266034, Shandong, China.

出版信息

Compr Psychiatry. 2020 Nov;103:152209. doi: 10.1016/j.comppsych.2020.152209. Epub 2020 Sep 30.

Abstract

BACKGROUND

In neonatal rats, MK-801 treatments can produce schizophrenia-like symptoms. Crocin is a water soluble carotenoid in Saffron that exerts potent neuroprotective effects. This work aimed to demonstrate the function of crocin in the alleviation of motor and cognitive impairments elicited by MK-801 in a neonatal rodent schizophrenia model, and to illustrate the underlying molecular mechanisms.

METHODS

Rats were treated with vehicle, MK-801 (1 mg/kg), MK-801 + 25 mg/kg crocin, or MK-801 + 50 mg/kg crocin. Motor learning and coordination, locomotion and exploratory activities, as well as spatial memory were assessed using the rotarod test, pen field test, and the Morris water maze test, respectively. Relative mRNA and protein levels of genes of interest were analyzed using qRT-PCR and Western blot assays, respectively.

RESULTS

In the hippocampus of rats with MK-801-elicited schizophrenia, administration of crocin elevated the expression of silent information regulator-1 (SIRT1) and brain derived neurotrophic factor (BDNF), and relieved the oxidative stress. The learning deficits and motor perturbations caused by MK-801 treatments were also alleviated by the crocin administration.

CONCLUSION

Collectively, crocin has exerted neuroprotective effects in the rat model of MK-801-elicited schizophrenia, via regulations of SIRT1 and downstream BDNF expression in the hippocampus.

摘要

背景

在新生大鼠中,MK-801 处理可产生类似精神分裂症的症状。西红花中的藏红花酸是一种水溶性类胡萝卜素,具有很强的神经保护作用。本研究旨在证明藏红花酸在缓解 MK-801 诱导的新生啮齿动物精神分裂症模型中的运动和认知障碍中的作用,并阐明其潜在的分子机制。

方法

大鼠分别用 vehicle、MK-801(1mg/kg)、MK-801+25mg/kg 西红花酸或 MK-801+50mg/kg 西红花酸处理。通过转棒试验、笔式试验和 Morris 水迷宫试验分别评估运动学习和协调、运动和探索活动以及空间记忆。使用 qRT-PCR 和 Western blot 分析相对基因和蛋白水平。

结果

在 MK-801 诱导的精神分裂症大鼠海马体中,藏红花酸可上调沉默信息调节因子 1(SIRT1)和脑源性神经营养因子(BDNF)的表达,缓解氧化应激。藏红花酸的给药还减轻了 MK-801 处理引起的学习和运动障碍。

结论

综上所述,藏红花酸通过调节海马体中的 SIRT1 和下游 BDNF 表达,对 MK-801 诱导的精神分裂症大鼠模型发挥了神经保护作用。

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