Comparative evolutionary studies on the expmssion of dementia-related genes in aging nonhuman animals

老年非人类动物痴呆相关基因表达的比较进化研究

• 批准号: 14360188
• 负责人: NAKAYAMA Hiroyuki
• 金额: $ 6.21万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14360188/
• 关键词: Amyloid beta; APP; Computer; Mammals; Brain; Microarray; Aging; Senile plaques; 老人班

We examined the immunohistochemical localization of beta-amyloid (A beta) and beta-amyloid precursor protein (APP) in the neuronal and non-neuronal tissues of dogs. A beta was detected only in the senile plaque (SP) in cerebrum of aged dogs. APP was expressed in the neuronal cell body and fiber independent of the age. In addition, glandular epithelial cells were immunopositive for APP. Thus, it is suggested that APP may be expressed in the non-neuronal epithelial tissues in dogs.Gene expressions of the canine brain was investigated using array membrane filters prepared for human analysis. Brain aging-related genes were upregulated in the brain from aged dogs. However, the expression of the APP gene was not increased in the aged brains.An attempt to create SPs of various shapes in silica was performed, using computer software programs. The resultant structures were morphologically evaluated by the fractal dimension (FD) method. SPs with low FD seemed to be smaller in size and less dense than those with higher FD. The low-FD SPs in silico may correspond to feline SPs in vivo, and the high-FD SP in silico to SPs of other animal species. According to the present results, SP formation in the aged feline brain may be different from that of other animal species, indicating a special A beta deposition process in cats.APP may play an important function(s) in the brain and some glandular tissues, and may be abnormally degraded to A beat in the brain by aging in dogs. However, the expression of APP was stable during life. Such abnormal degradation of APP and the inhibition of A betalysis may be crucial for A beta deposition in the canine brain.

我们研究了β-淀粉样蛋白（A β）和β-淀粉样蛋白前体蛋白（APP）在狗的神经元和非神经元组织中的免疫组织化学定位。A β仅在老年犬大脑的老年斑中检出。APP在神经元胞体和纤维中的表达与年龄无关。此外，腺上皮细胞的APP的免疫阳性。因此，这表明，APP可能是在非神经元上皮组织在dogs.Gene表达的狗脑进行了研究，使用阵列膜过滤器制备的人类分析。脑老化相关基因在老年犬的脑中上调。然而，APP基因的表达在老年人的大脑中并没有增加。通过分形维数（FD）方法对所得结构进行了形态学评价。低FD的SP似乎比高FD的SP更小，密度更低。计算机模拟的低FD SP可能对应于体内猫SP，计算机模拟的高FD SP可能对应于其他动物物种的SP。根据本研究结果，猫脑中SP的形成可能不同于其他动物，提示猫脑中有一种特殊的A β沉积过程，APP可能在脑和某些腺体组织中起重要作用，并可能在狗脑中因衰老而异常降解为A β。而APP的表达在整个生命过程中是稳定的。APP的这种异常降解和A β分析的抑制可能对犬脑中的A β沉积至关重要。

项目成果

中山裕之: "イヌに痴呆はありますか?"Clinical Neuroscience (臨床神経科学). 第20巻. 487 (2002)

Hiroyuki Nakayama：“狗有痴呆症吗？” 20. 487 (2002)

Immunohistochemical detaction of beta-amyloid precursor protein in the canine brain and non-neuronal epithelial tissues

犬脑和非神经上皮组织中β-淀粉样前体蛋白的免疫组织化学检测

• 发表时间: 2004
• 期刊: Amyloid 11
• 作者: Fukuoka;A.;Nakayama;H.;Doi;K.
• 通讯作者: K.

中山裕之: "老齢性脳病変の進化病理学的考察-動物に神経変性疾患はあるのか-"獣医神経病. 第8号(実際の発刊は2002年). 3-9 (2001)

Hiroyuki Nakayama：“老年脑损伤的进化病理学考虑 - 动物中是否存在神经退行性疾病？”第 8 期（实际发表于 2002 年 3-9 期）。

Fukuoka, A., Nakayama, H., Doi, K.: "Immunohistochemical detection of β-amyloid and β-amyloid precursor protein in the canine brain and non-neuronal epithelial tissues."Amyloid. (in press). (2004)

Fukuoka, A.、Nakayama, H.、Doi, K.：“犬脑和非神经上皮组织中 β-淀粉样蛋白和 β-淀粉样蛋白前体蛋白的免疫组织化学检测。”淀粉样蛋白（2004 年出版）。

Age-related histological changes in the canine substantia nigra.

犬黑质与年龄相关的组织学变化。

• 发表时间: 2003
• 期刊: J.Vet.Med. Sci 65
• 作者: Uchida;K.;Kihara;N.;Hashimoto;K.;Nakayama et al.
• 通讯作者: Nakayama et al.