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白藜芦醇,一种SIRT1激活剂,可改善MK-801诱导的精神分裂症新生大鼠模型的认知和运动障碍。

Resveratrol, a SIRT1 Activator, Ameliorates MK-801-Induced Cognitive and Motor Impairments in a Neonatal Rat Model of Schizophrenia.

作者信息

Niu Juan, Cao Yuquan, Ji Yongjuan

机构信息

Psychological Clinic, The Affiliated Hospital of Qingdao University, Qingdao, China.

Rizhao Mental Health Center, Rizhao, China.

出版信息

Front Psychiatry. 2020 Jul 24;11:716. doi: 10.3389/fpsyt.2020.00716. eCollection 2020.

Abstract

BACKGROUND

In neonatal rats, MK-801 treatment generates schizophrenia-like symptoms. Resveratrol (RSV) is a phenolic compound and a potent neuroprotective agent. This research aimed to illustrate the effect of RSV on the amelioration of MK-801-induced cognitive and motor impairments in a neonatal rat schizophrenia model and the related potential molecular changes.

METHODS

Rats were administrated with MK-801, MK-801 + RSV (40 mg/kg), or MK-801 + RSV (80 mg/kg). Motor learning, coordination, locomotor and exploratory activity, and spatial memory were measured by rotarod test, pen field test, and Morris water maze test. Relative protein levels were analyzed by Western blot and ELISA. mRNA levels were shown by qRT-PCR.

RESULTS

In the hippocampus of MK-801-induced schizophrenia rat model, RSV enhanced silent information regulator 1 (SIRT1) and brain derived neurotrophic factor (BDNF) expression and alleviated oxidative stress. Motor perturbations and learning impairments by MK-801 treatment were ameliorated by the administration of RSV.

CONCLUSION

In conclusion, RSV showed neuroprotective effect on MK-801-induced schizophrenia rat model through regulating SIRT1 and downstream BDNF expression in the hippocampus.

摘要

背景

在新生大鼠中,给予MK-801会产生类似精神分裂症的症状。白藜芦醇(RSV)是一种酚类化合物,是一种有效的神经保护剂。本研究旨在阐明RSV对新生大鼠精神分裂症模型中MK-801诱导的认知和运动障碍的改善作用以及相关的潜在分子变化。

方法

将大鼠分为三组,分别给予MK-801、MK-801 + RSV(40 mg/kg)或MK-801 + RSV(80 mg/kg)。通过转棒试验、旷场试验和莫里斯水迷宫试验测量运动学习、协调、运动和探索活动以及空间记忆。通过蛋白质免疫印迹法和酶联免疫吸附测定法分析相关蛋白水平。通过实时定量聚合酶链反应显示mRNA水平。

结果

在MK-801诱导的精神分裂症大鼠模型的海马中,RSV增强了沉默信息调节因子1(SIRT1)和脑源性神经营养因子(BDNF)的表达,并减轻了氧化应激。给予RSV可改善MK-801治疗引起的运动障碍和学习障碍。

结论

总之,RSV通过调节海马中SIRT1和下游BDNF的表达,对MK-801诱导的精神分裂症大鼠模型具有神经保护作用。

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