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脑内注射链脲佐菌素以建立大鼠阿尔茨海默病模型

Intracerebral Injection of Streptozotocin to Model Alzheimer Disease in Rats.

作者信息

Moreira-Silva Daniel, Vizin Robson C L, Martins Talita M S, Ferreira Tatiana L, Almeida Maria C, Carrettiero Daniel C

机构信息

Graduate Program in Neuroscience and Cognition, Federal University of ABC, São Bernardo do Campo, Brazil.

Undergraduate Program in Neuroscience, Federal University of ABC, São Bernardo do Campo, Brazil.

出版信息

Bio Protoc. 2019 Oct 20;9(20):e3397. doi: 10.21769/BioProtoc.3397.

Abstract

Animal models have promoted meaningful contribution to science including Alzheimer's disease (AD) research. Several animal models for AD have been used, most of them related to genetic mutations observed in familial AD. However, sporadic form of AD, also named late-onset is the most frequent form of the disease, which is multifactorial, being influenced by genetic, environmental and lifestyle factors. Here, we describe a protocol of an AD-like pathology of the sporadic form using Wistar rats by a single bilateral intracerebroventricular (icv) injection of streptozotocin (STZ, 2 mg/kg). Icv injection of STZ induces brain resistance to insulin and other pathological alterations related to those observed in AD, such as cognitive impairment and accumulation of phosphorylated tau protein and β-amyloid in the brain. Thus, icv injection of STZ is a useful tool to investigate the pathological mechanisms and the metabolic alterations involved in AD and to propose new therapeutic approaches and neuroprotective drugs.

摘要

动物模型对包括阿尔茨海默病(AD)研究在内的科学领域做出了有意义的贡献。已经使用了几种AD动物模型,其中大多数与家族性AD中观察到的基因突变有关。然而,散发性AD,也称为晚发性AD,是该疾病最常见的形式,它是多因素的,受遗传、环境和生活方式因素影响。在这里,我们描述了一种使用Wistar大鼠通过单次双侧脑室内(icv)注射链脲佐菌素(STZ,2 mg/kg)来诱导散发性AD样病理的方案。脑室内注射STZ会诱导大脑对胰岛素产生抵抗以及出现与AD中观察到的其他病理改变,如认知障碍以及大脑中磷酸化tau蛋白和β-淀粉样蛋白的积累。因此,脑室内注射STZ是一种有用的工具,可用于研究AD涉及的病理机制和代谢改变,并提出新的治疗方法和神经保护药物。

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