PET Applications in Animal Models of Neurodegenerative and Neuroinflammatory Disorders
PET Applications in Animal Models of Neurodegenerative and Neuroinflammatory Disorders
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PET 在神经退行性和神经炎症性疾病动物模型中的应用
DOI：
10.1007/7854_2011_167
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Suhara T
中科院分区：
文献类型：
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作者：
Higuchi M;Maeda J;Ji B;Tokunaga M;Zhang MR;Maruyama M;Ono M;Fukumura T;Suhara T
对家族性阿尔茨海默氏病 (AD) 等遗传性神经系统疾病的研究揭示了导致神经退行性变的致病蛋白异常，而散发性神经精神疾病的分子引发剂仍未确定。此类疾病的特征是分子异常的集合，这些异常可能与神经元的突触功能障碍和其他退化密切相关。为正电子发射断层扫描 (PET) 成像设计的各类放射化学物质通过跟踪这些过程中关键分子的时空相关性，有助于描绘这些过程中关键分子之间的机械联系。鉴于啮齿动物和非人类灵长类动物模型适合侵入性遗传和药理学干预，这种测定技术特别有用。此外，当与侵入性的生前和死后研究（例如体内微透析、电生理学和组织病理学技术）相结合时，PET 对神经化学和神经病理学变化的检测可以在实验室动物中进行检查。本综述主要涵盖使用 PET 来阐明脑部疾病的小动物模型来阐明病因分子级联，从而促进寻找适用于人类 AD 和相关疾病的诊断和治疗药物。
Studies on hereditary neurological disorders such as familial Alzheimer’s disease (AD) have revealed abnormalities of pathogenic proteins causative of neurodegeneration, while molecular initiators of sporadic neuropsychiatric conditions remain unidentified. Such disorders are characterized by collections of molecular abnormalities that may be critically involved in synaptic dysfunctions and other deteriorations in neurons. Diverse classes of radiochemicals designed for positron emission tomographic (PET) imaging facilitate delineation of mechanistic links among key molecules in these processes by tracking their spatiotemporal correlations. This assay technique is of particular utility when applied to rodent and nonhuman primate models given their suitability for invasive genetic and pharmacological interventions. In addition, the detection of neurochemical and neuropathological changes by PET can be examined in laboratory animals when combined with invasive antemortem and postmortem investigations such as in vivo microdialysis, electrophysiological and histopathological techniques. This review primarily covers the use of small animal models of brain disorders using PET to elucidate etiological molecular cascades to facilitate in turn the search for diagnostic and therapeutic agents applicable to AD and related disorders in humans.