Neurogenic control of cerebrovascular bed : Study of Klotho type mouse

Klotho基因表达缺陷导致一种类似人类衰老的综合征，包括寿命短、不孕不育、动脉硬化、皮肤萎缩、骨质疏松和肺气肿。与野鼠相比，Klotho小鼠的神经组织学、生理和脑代谢参数进行了研究。i)组织学和生理学研究；Klotho小鼠的新皮质和下丘脑中神经元、轴突和S-100染色稀疏。Klotho小鼠(4周龄和6周龄)体重明显减轻，血糖明显降低。ii)局部脑葡萄糖利用(LCGU)；在初步实验的基础上，我们将改进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、45min腹腔注射30μ2dG的Ci，并对5例μL尾端混合血样进行校正。低血糖小鼠的集总常数以前是在低血糖大鼠身上测定的(苏达等人，1990)。(1)4周龄LCGU(W.O.)Klotho型(KL/KL)组与野生型(+/+)组比较，丘脑、尾壳核、下丘、小脑皮质和内盖的LCGU无明显变化。(2)6周龄小鼠的LCGU，Klotho(KL/KL)与野生(+/+)相比，全脑LCGU显著低于野生小鼠。(3)4周龄小鼠葡萄糖利用率比较。和6个W.O.Klotho型小鼠的6W.O显著降低。在我们以前的研究中，我们认为基底前脑在脑血管床的控制中起着重要的作用。年轻Klotho小鼠对这些特定区域的葡萄糖利用仍有待进一步研究。

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.