Confirmation of animal models to clarify mechanism of dementia and to develop anti-dementia drugs

确认动物模型以阐明痴呆机制并开发抗痴呆药物

• 批准号: 12556054
• 负责人: NAKAYAMA Hiroyuki
• 金额: $ 6.91万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12556054/
• 关键词: Animals; fractal dimension; Senile plaques; Amyloid beta; Three-dimensinnal analysis; 遺伝子発現; 神経原線維変化; 脳; 比較進化学; 老化; アミロイドβタンパク質; フラクタル; プリセニリン

1. Fractal dimension (FD) of senile plaques (SP) of various animal species were calculated and compared. FDs between diffuse (DP) and mature (MP) plaques were significantly different in the dog, monkey and human. In the dog. The FD value and size of SP were plotted. Significant difference was shown between the slope values of the lines of DP and MP. DP and MP were differently formed in these animals. The FD of feline DP was less than those of the dog, monkey, bear, camel and human, indicating special characteristics of feline SP.2. SPs of aged dogs were three-dimensionally (3D) observed. An assembly of amyloid beta (A β) protein of DP was uneven nebula-like structure and that of MP was membrane-like or filamentous one. There were areas of low-density A β deposition inside DP and MP. 3D distribution of amyloid precursor protein, ubiqiutin, glial fibrillary acidic protein and neurofilament were also examined, The results indicated that the two types of SP are formed separately.3. 3D pattern and fractal dimension of assemblies of the two A/β subspecies, I.e. A/β40 and A β42, were investigated. The processes of the 2 types of A β were clarified to be different.4. The distribution of presenilin 1 (PS1) protein in the brain of the eynomoIgus monkey was examined. Carboxyl terminal of PS1 was detected in the cortical neuropil and the deposition was increased with age. The results of the present studies revealed the brain lesions of aged animals. Further, important paradigms in the field of comparative biology such as "SPs are formed but neurofibrilliary tangles are not formed in the nonhuman animals" have been clarified.

1.计算并比较了不同种属动物衰老斑块的分维。狗、猴和人的弥漫性斑块(DP)和成熟斑块(MP)之间的FDD有显著差异。在狗身上。绘制出Fd值和SP的大小。DP和MP系的斜率值有显著差异。在这些动物中，DP和MP的形成方式不同。猫DP的FD小于狗、猴、熊、骆驼和人，显示了猫SP的特殊性。对老年犬SPS进行三维(3D)观察。DP的淀粉样β蛋白(Aβ)呈不均匀的星云状结构，MP的淀粉样β蛋白呈膜状或丝状。DP和MP内有低密度的A-β沉积。同时还观察了淀粉样前体蛋白、泛素、胶质纤维酸性蛋白和神经丝的三维分布，结果表明这两种类型的SP是分别形成的。研究了A/β40和Aβ42两个A/β亚种的三维构型和集合体的分维。阐明了两种类型的A-β的加工过程不同。观察了早老素1(PS1)蛋白在恒河猴脑内的分布。PS1的羧基末端存在于皮质神经管中，并随年龄的增长而增加。本研究的结果揭示了老年动物的脑损伤。此外，还澄清了比较生物学领域中的重要范式，如在非人类动物中形成了SPS，但没有形成神经纤维缠结。

项目成果

Nakayama, H., Yoshikawa, Y., Doi, K. et al: "Fractal analysis of senile plaques observed in various animal species"Neuroscience Letters. 297. 195-198 (2001)

Nakayama, H.、Yoshikawa, Y.、Doi, K. 等人：“在各种动物物种中观察到的老年斑的分形分析”神经科学快报。

Nakayama, H.: "An evolutionary study of age-related brain pathology―Are neurodegenerative diseases present in nonhuman anirnals ?"Journal of Japanese Veterinary Neurology (In Japanese). 8. 3-9 (2001)

Nakayama, H.：“年龄相关脑病理学的进化研究——非人类动物中是否存在神经退行性疾病？”日本兽医神经病学杂志（日文）。

Miyawaki,K.,Makayama,H.,Nakamura,S.,Doi,K.: "Three-dimensional structures of canine senile plaques."Acta Neuropathologica. (印刷中). (2001)

Miyawaki, K.、Makayama, H.、Nakamura, S.、Doi, K.：“犬老年斑的三维结构”。神经病理学报（2001 年出版）。

Samura.E., Nakayama,H., Doi,K., Yoshikawa,Y., et al: "Biological and immunohistochemical studies of amyloid β protein (A β) species in aged canine brains"Brain Research. in preparation.

Samura.E.、Nakayama,H.、Doi,K.、Yoshikawa,Y. 等人：“老年犬脑中淀粉样 β 蛋白 (A β) 种类的生物学和免疫组织化学研究”大脑研究准备中。

Nakayama, H., Yoshikawa, Y., Doi, K.他: "Fractal anaylysis of senile plagues observed in various animal species"Neuroscience Letters. 297. 195-198 (2001)

Nakayama, H.、Yoshikawa, Y.、Doi, K. 等人：“在各种动物物种中观察到的老年瘟疫的分形分析”《神经科学快报》297. 195-198 (2001)。