MORI Kentaro Juntendo University, Dept of Neurosurgery, Associate Professor, 医学部, 助教授 (30200364)
YAMAMOTO Takuji Juntendo University, Dept of Neurosurgery, Assistant Professor, 医学部, 講師 (50255684)
NAKAO Yasuaki Juntendo University, Dept of Neurosurgery, Assistant Professor, 医学部, 講師 (50271276)
|Budget Amount *help
¥2,900,000 (Direct Cost : ¥2,900,000)
Fiscal Year 2005 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2004 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2003 : ¥1,700,000 (Direct Cost : ¥1,700,000)
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.