Comparative studies on beta amyloid deposition and brain aging

β淀粉样蛋白沉积与脑衰老的比较研究

• 批准号: 17380185
• 负责人: NAKAYAMA Hiroyuki
• 金额: $ 7.28万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17380185/
• 关键词: Dog; Cat; Microarray; Nprilysin; Beta amyloid(A beta); MPTP; Brain; Prion model; マウス; ウシ; パーキンソン病モデル; BSEモデル; 老化; 神経幹細胞アポトーシス; 犬; 猫

We first investigated total gene expressions in the canine brain using a microarray system. Genes upregulated were GFAP, CNPase and p35, and those downregulated were APP and Tau.Activities "and expressions of neprilysin (Nep) and depositions of beta amyloid (A beta) were examined in the canine and feline brains. Nep was weakly expressed in the cerebral cortex and strongly in the striatum and substantia nigra (SN) in both animals. Activities of Nep were higher in the order of striatum > cerebral cortex > white matter / hippocampus. Nep activity and expression were not related to aging, although Nep activity was tended to decrease in the canine striatum with age. A beta deposition was increased with age in both dogs and cats.Strain difference of the neuronal cell loss was investigated in MPTP-treated C57BL/6 mice which is a Parkinson's disease model. Tyrosine hydroxylase (TH) expression in the SN-striatum was decreased in C57BL/6 mice but not in BALB/c mice. Some mice showed such decrease of HT expression in non-inbred ICR mice. It was therefore suggested that a single gene would be involved in the expression of the disease in the MPTP-treated Parkinson model mice.Fusion protein of green fluorescent protein (GFP) and A beta has been massively produced. The GFP-A beta was administered orally into juvenile mice and cows before or after weaning. GFP-A beta reached to the jejunum and ileum without degradation in the stomach, and incorporated through the absorptive epithelium in the villi of both species. The incorporation occurred in the suckling period. This experimental system would be an excellent model to investigate the intestinal invasion of prion protein.

我们首先使用微阵列系统研究了犬脑中的总基因表达。上调的基因有GFAP、CNPase和p35，下调的基因有APP和Tau。在犬和猫的大脑中检测了Nep蛋白的活性和表达以及β淀粉样蛋白的沉积。Nep在两种动物的大脑皮层中表达较弱，在纹状体和黑质（SN）中表达较强。脑皮层>白质/海马纹状体>活性较高。犬纹状体Nep活性随年龄的增长呈下降趋势，但其活性和表达与衰老无关。狗和猫的β沉积随着年龄的增长而增加。观察mptp处理的C57BL/6帕金森病模型小鼠神经元细胞损失的品系差异。C57BL/6小鼠sn纹状体中酪氨酸羟化酶（TH）表达降低，BALB/c小鼠则无此现象。部分小鼠在非近交ICR小鼠中HT表达明显降低。因此，在mptp治疗的帕金森模型小鼠中，可能有一个基因参与了疾病的表达。绿色荧光蛋白（GFP）与A β的融合蛋白已大量生产。GFP-A β分别在断奶前和断奶后口服给药。GFP-A β到达空肠和回肠而没有在胃中降解，并通过绒毛的吸收上皮结合。合并发生在哺乳期。该实验系统为研究朊病毒蛋白的肠道侵袭提供了良好的模型。

项目成果

Neural progenitor cells are protected against MPTP by MAO-B inhibitors

• DOI: 10.1016/j.neuro.2008.05.009
• 发表时间: 2008-11-01
• 期刊: NEUROTOXICOLOGY
• 影响因子: 3.4
• 作者: He, Xi Jun;Uetsuka, Koji;Nakayama, Hiroyuki
• 通讯作者: Nakayama, Hiroyuki

動物にアルツハイマ-病はあるのか-老齢犬の脳病変から老化の進化を考える-

动物中是否存在阿尔茨海默病？ - 思考老年狗大脑损伤的衰老演变 -

• 发表时间: 2006
• 期刊: Biophilia 2
• 作者: He;X.-J.;Nakayama;H.;中山裕之
• 通讯作者: 中山裕之

離乳移行期における経口投与アミロイド蛋白の腸管での取込み

断奶过渡期口服淀粉样蛋白的肠道摄取

• 发表时间: 2008
• 作者: 阿野泰久;中山裕之;作道章一;眞鍋昇;小野寺節
• 通讯作者: 小野寺節

アミロイド変性の組織学-鳥類のアミロイド症-

淀粉样变性的组织学 - 鸟类淀粉样变性 -

• 发表时间: 2005
• 作者: He;X. J.;Nakayama;H.;Yamauchi;H.;Uetsuka K.;Doi K.;中山裕之
• 通讯作者: 中山裕之

Neural progenitor cells are protected against MPTP by MAO-B inbititors

MAO-B 抑制剂可保护神经祖细胞免受 MPTP 侵害

• 发表时间: 2008
• 期刊: submitted to Neurotoxicol
• 作者: He. X. J.;Uetsuka;K.;Nakayama;H.
• 通讯作者: H.