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Neurogenic control of cerebrovascular bed : Study of Klotho type mouse

脑血管床的神经源性控制：Klotho型小鼠的研究

基本信息

批准号：
15591550
负责人：
MAEDA Minoru
金额：
$ 1.86万
依托单位：
Juntendo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591550/
关键词：
Klotho mouse Wild mouse 4 weeks and 6 weeks old [^<14>C]DG LCGU Nuerogeneric control of cerebrovascular bed basal forebrain 脳の組織学的変化

项目摘要

A defect in klotho gene expression in the mouse results in a syndrome that resembles human ageing, including a short life span, inferitility, arteriosclerosis, skin atrophy, osteoporosis and emphysema.Neurohistological, physiological and cerebral metabolic parameters were investigated in the klotho mouse in comparison with the wild mouse.i) Histological and physiological studies ; In the klotho mice, neurons, axons and S-100 stain were sparse in the neocortex and the hypocampus. The klotho mice (both in 4 weeks and 6 weeks old) were significantly light in weight and low in blood sugar.ii) Local cerebral glucose utilization (LCGU) ; On the base of preliminary experiments, we applied the modified deoxyglucose method to the wild and transgenic mice. 30μCi of 2DG was injected intraperitoneally and 5μL mixed blood samples from the cut end of tail were corrected at 0, 10, 20, 30 and 45 minutes. The lumped constants for hypoglycemic mice were previously determined in the hypoglycemic rat (Suda et al, 1990).(1) LCGU of 4 weeks old (w.o.) mice ; klotho type (kl/kl) vs wild type (+/+), LCGU in the thalamus, caudate putamen, inferior colliculus, cerebellar cortex and internal capsel of the klotho mice were not significantly changed. LCGU in the other structures including neocortex were significantly decreased in comparison with the wild mice.(2) LCGU of 6 weeks old mice ; klotho (kl/kl) vs wild (+/+), LCGU in whole brain of the klotho mice were significantly, remarkably lower than those of the wild mice.(3) The comparison of glucose utilization of 4 w.o. and 6 w.o. mice in klotho type revealed significant decrease in 6 w.o. mice.iii) In our previous studies, it is proposed that the basal forebrain plays an important role for control of cerebrovascular bed. Glucose utilization of these specific areas in younger klotho mice remaines to be further investegation.

老鼠体内的klotho基因表达缺陷会导致一种类似人类衰老的综合症，包括寿命缩短、不孕不育、动脉硬化、皮肤萎缩、骨质疏松和肺气肿。研究了klotho小鼠的神经组织学、生理和脑代谢参数，并与野生小鼠进行了比较。i)组织学和生理学研究；klotho小鼠新皮层和下丘脑神经元、轴突和S-100染色稀疏。klotho小鼠（4周龄和6周龄）体重明显轻，血糖明显低。ii)局部脑葡萄糖利用率（LCGU）；在初步实验的基础上，将改良的脱氧葡萄糖方法应用于野生小鼠和转基因小鼠。分别于0、10、20、30、45分钟，腹腔注射2DG 30μ ci，尾切端取5μL混合血进行校正。低血糖小鼠的集总常数是先前在低血糖大鼠中确定的（Suda et al, 1990）。(1) 4周龄小鼠LCGU；klotho型（kl/kl）与野生型（+/+）相比，klotho小鼠的丘脑、尾状壳核、下丘、小脑皮质和内囊的LCGU均无显著变化。与野生小鼠相比，包括新皮层在内的其他结构LCGU明显减少。(2) 6周龄小鼠LCGU；klotho (kl/kl) vs野生（+/+），klotho小鼠全脑LCGU显著低于野生小鼠。(3)与klotho型小鼠相比，4只w.o.和6只w.o.小鼠的葡萄糖利用率明显降低。iii)在我们之前的研究中，提出基底前脑在脑血管床的控制中起重要作用。年轻klotho小鼠这些特定区域的葡萄糖利用仍有待进一步研究。