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东莨菪碱诱导的神经化学特征更大改变及氧化应激增加表明其是一种更好的痴呆模型:一项比较研究。

Scopolamine-induced greater alterations in neurochemical profile and increased oxidative stress demonstrated a better model of dementia: A comparative study.

作者信息

Haider Saida, Tabassum Saiqa, Perveen Tahira

机构信息

Neuropharmacology And Neurochemistry Research Unit, Department of Biochemistry, University of Karachi, Karachi, 75270, Pakistan.

Neuropharmacology And Neurochemistry Research Unit, Department of Biochemistry, University of Karachi, Karachi, 75270, Pakistan.

出版信息

Brain Res Bull. 2016 Oct;127:234-247. doi: 10.1016/j.brainresbull.2016.10.002. Epub 2016 Oct 8.

Abstract

Cognitive decline is found to be a common feature of various neurological disorders like Alzheimer's disease (AD). In order to recapitulate AD associated cognitive deficits and to plan therapeutic strategies researchers have developed various preclinical dementia models to recapitulate different aspects of cognitive domains affected in AD brain. So, the present study was aimed to compare alterations in previously reported dementia models i.e. pharmacological (Scopolamine-induced and corticosterone-induced), Environmental (Aluminium-induced and noise-stress) and physiological (natural aging) models in rats in a single experimental study across three cognitive domains spatial, recognition, and associative memory and associated alterations in their oxidative status and neurochemical profile to select appropriate dementia model. All groups received their respective treatments for 14days after which behavioural analysis was performed including Open Field test to assess ambulatory activity, Novel Object Recognition test, Morris Water Maze test and Passive Avoidance test for the assessment of recognition, spatial and associative memory. After monitoring the behavioural activities, rats were decapitated and their brains and hippocampus samples were collected for analysis of oxidative status and neurochemical profile. Results showed significant decline in different aspects of memory function in all dementia models which was more significant in scopolamine-injected rats. A significant decline in levels of monoamines and acetylcholine was also observed. In addition, significant alterations were also seen in oxidative profile indicating that cognitive decline could be associated with increased oxidative stress. Therefore, present findings highlight that for planning therapeutic strategies against cognitive dysfunctions, scopolamine-induced dementia model is the most appropriate dementia model to reveal AD-related cognitive impairment profile.

摘要

认知衰退被发现是各种神经疾病(如阿尔茨海默病(AD))的一个常见特征。为了重现与AD相关的认知缺陷并制定治疗策略,研究人员开发了各种临床前痴呆模型,以重现AD大脑中受影响的认知领域的不同方面。因此,本研究旨在比较先前报道的痴呆模型(即药理学模型(东莨菪碱诱导和皮质酮诱导)、环境模型(铝诱导和噪声应激)和生理学模型(自然衰老))在大鼠中的变化,在一项单一实验研究中跨越空间、识别和联想记忆这三个认知领域,并比较它们氧化状态和神经化学特征的相关变化,以选择合适的痴呆模型。所有组接受各自的治疗14天,之后进行行为分析,包括用于评估自主活动的旷场试验、用于评估识别、空间和联想记忆的新物体识别试验、莫里斯水迷宫试验和被动回避试验。在监测行为活动后,将大鼠断头,并收集它们的大脑和海马样本,用于分析氧化状态和神经化学特征。结果显示,所有痴呆模型的记忆功能的不同方面均显著下降,在注射东莨菪碱的大鼠中更为显著。还观察到单胺和乙酰胆碱水平显著下降。此外,氧化特征也有显著变化,表明认知衰退可能与氧化应激增加有关。因此,目前的研究结果突出表明,为了制定针对认知功能障碍的治疗策略,东莨菪碱诱导的痴呆模型是揭示AD相关认知障碍特征的最合适的痴呆模型。

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